1 The Application of Transgenesis to Abraham Trembley’s Hydra, an Ancient Animal Model for the Study of Regeneration that has now entered the 21st Century , Michael P Sarras Jr*
Developmental biology and regenerative biology began with the studies of Abraham Trembley who was a mathematician. Trembley initiated studies with the freshwater hydrozoan, hydra to determine if the organism was a plant or animal. His first studies in 1740 found that bisection of the organism lead to the formation of two complete adult appearing hydra and he then proceeded to perform extensive experiments to evaluate the extent of hydra’s “regenerative capabilities”. He performed numerous experiments that culminated in the publication of his book in 1744 on the biology and regenerative nature of hydra. His studies established the early foundations of regenerative biology that have been built upon over the years and has led to current studies focusing on cellular and molecular mechanisms. From Trembley’s initial studies, regenerative biology has grown to encompass the field of regenerative medicine that applies our understanding of regenerative processes to the human condition.
2 Local Anesthetics Can Affect the Efficacy of Telomerase-Positive Stem Cells , Henry E Young1-3*, Mark O Speight4-6
Early clinical studies with telomerase-positive stem cells demonstrated no response when these stem cells were mixed with lidocaine prior to clinical treatments in multiple individuals. Their stem cells demonstrated a positive response when mixed with normal sterile saline utilizing alternative routes of implantation. We hypothesized that lidocaine killed the stem cells before injection and that dead stem cells would give no response. We tested five local anesthetics, e.g., bupivacaine, lidocaine, marcaine, novocaine and procaine, with sterile saline in a series of blinded experiments to determine their ability to affect the viability of telomerase-positive stem cells. A mixture of TSCs, PSCs and MesoSCs were utilized from five individuals, three males and two females. Trypan blue was used to distinguish live versus dead PSCs and MesoSCs. The number of dead cells divided by total number of cells and multiplied by 100 was used for each test solution to determine their respective % kill ratio. Sample size was n=180 for each test solution. Lidocaine demonstrated a 100% kill ratio; novocaine and procaine demonstrated a 50% kill ratio and marcaine, bupivacaine and sterile saline demonstrated a 0% kill ratio. The results showed that lidocaine should not be used with telomerase-positive stem cells for clinical treatments.
3 Informed Consent Guidelines for Optimizing the Use of Telomerase-Positive Stem Cells , Henry E Young1-3*, Mark O Speight4-6
The objectives of the work, based on previous characterization studies, pre-clinical animal models of induced diseases, e.g., Parkinson disease, cardiovascular disease, pulmonary disease, and type-I diabetes mellitus, and early clinical human studies of Parkinson disease, cardiovascular disease, and pulmonary diseases, were to established a set of criteria that needed to be followed for using telomerase-positive stem cells in future human clinical trials. From this set of criteria, informed consent guidelines were established to optimize the safety and efficacy of using endogenous adult-derived telomerase-positive stem cells to restore organ function by either repair and/or regeneration of cells and tissues resulting from tissue damage and/or loss. Inclusion criteria were any male or female, 18 to 120 years of age, with preferably no serious comorbidities. Exclusion criteria were use of alcohol, tobacco products, vaping, recreational drugs, lidocaine, and/or chemotherapeutic drugs. We also cautioned use of caffeine and corticosteroids, as well as limiting moderate to strenuous physical activity within a two-week window before and after stem cell treatment. Following these inclusion and exclusion criteria, endogenous adult-derived autologous and/or allogeneic telomerase-positive stem cells have proven to be both safe and effective at restoring (up to 50% above pre-treatment values in compliant individuals) organ function for diseases and/or disorders caused by trauma or chronic diseases. Conditions treated thus far, within IRB-approved human study protocols, include neurodegenerative, cardiovascular, pulmonary, autoimmune, renal, and orthopedic disorders.
4 Management of Resistant Endometrium in Cases of Recurrent Implantation Failure Using Endometrial Mesenchymal Stem Cells as an Innovative Regenerative Therapy-A Short Communication , Kulvinder Kochar Kaur1*, Gautam Allahbadia2, Mandeep Singh3
Currently the most accepted definition of Recurrent Implantation Failure (RIF) ,is the absence of achieving clinical pregnancy following transfer of 3 or more good quality embryos in women under 35 years age as well as 4 or in ≥ 35 years age women in fresh or frozen ET’s We had reviewed earlier comprehensively how to manage the endometrial factor in cases of RIF utilizing antibiotics not only orally but further using intrauterine antibiotics and then Platelet Rich Plasma (PRP).Despite that there are certain cases that refuse to respond .We have further delved deeper into pathophysiology of Recurrent Implantation Failure (RIF) along with describing innovatively the use of Mesenchymal Stem Cells (MSCs) cells derived from endometrial stem cells in 29 cases of RIF mixed with PRP that was successful in 23/29 cases besides improving Endometrial Thickness (EMT), but further in Clinical Pregnancy (CP) as well as Live Birth Delivery Rates (LBDR). Further we describe the role of Platelet and Endothelial Cell Adhesion Molecule 1 (PECAM) along with Transforming Growth Factor Beta (TGFβ) besides CDYL in RIF.
5 Criteria to Distinguish Endogenous Telomerase-Positive Totipotent Stem Cells from Exosomes as Major Players in Regenerative Medicine , Henry E Young1-3*, Mark O Speight4-6
Endogenous adult-derived Totipotent Stem Cells (TSCs) and tissue-resident exosomes are major players in the field of regenerative medicine. TSCs provide the undifferentiated building blocks for tissue repair, while exosomes provide the directions on how these building blocks should be used to accomplish this feat, i.e., restoration of fully functional tissue. Both TSCs and exosomes have been extensively characterized with respect to composition and function. While they have similar characteristics in four categories, they differ with respect to each other in a myriad of other categories. The following is criteria used by this lab to distinguish telomerase-positive totipotent stem cells from bioactive factor-containing exosomes.
6 Patient Perspectives on Use of Stem Cells to Treat Osteoporosis , Hilary Isla Brown1, Tom Clutton-Brock2, Dawn-Marie Walker3, Opinder Sahota4, Brigitte E Scammell5, Ifty Ahmed6*
Osteoporosis is a systemic skeletal disease leading to increased risk of fragility fractures. These fractures lead to significant patient morbidity, increased mortality and substantial health and social care costs. The use of stem cells for cell-based therapies is currently an exciting, promising and growing area for disease treatment and regenerative medicine. However, the attitudes of participants towards the use of stem cells for regenerative medicine applications, particularly for therapeutic interventions amongst the older population, have not been well explored. This study explored patient perceptions of a proposed new treatment utilising a novel orthobiologic stem cell therapy. An online questionnaire for participants affected by osteoporosis was designed using the ‘Bristol Online Survey’ tool. In addition, three focus groups were held to explore a number of the issues raised by the findings in more depth. Findings showed that acceptability for the new treatment was high, as current treatments were variable in their effectiveness and new treatments were keenly welcomed. Participants indicated a willingness to have the proposed treatment in order to reduce their chance of experiencing a fracture, regardless of whether the treatment would reduce existing pain, or improve existing quality of life. The use of both autologous and allogeneic stem cells was acceptable, with slight differences in opinion indicating reservations regarding the potentially painful nature of stem cell extraction and allogeneic stem cell rejection. The findings demonstrated a clear mandate to the research team (and community) to continue their efforts in developing stem cell-based treatments for bone repair applications.
7 The Future Role of Mesenchymal Stem Cells in Tissue Repair and Medical Therapeutics: Realities and Expectations , Khalid A Al-Anazi1*
Mesenchymal Stem Cells (MSCs); which were first described by Alexander Fridenstein in the 1960s; are heterogeneous, non-hematopoietic, adult multipotent stromal progenitor cells that are capable of self-renewal and differentiation into various cell types [1-8]. They can be isolated from various sources including: Bone Marrow (BM) which is the main source, peripheral blood, umbilical cord blood, amniotic fluid, placenta, Adipose Tissue (AT), dental pulp, synovial fluid, salivary glands, liver, lung, skin and skeletal muscles [1-10]. MSCs have the following distinguishing features: adherence to the plastic vessel; capacity to different into osteoblasts, adipocytes and chondrocytes; and being characteristically positive for CD105, CD73, and CD90 and characteristically negative for CD45, CD34, CD11b, CD14, CD19, CD79a, and human leukocyte antigen (HLA)-DR on flow cytometry [1,3,4,11-16]. However, under certain circumstances, MSCs obtained from BM, AT, and other sources may express CD34 surface markers [5-8,17]. Additionally, MSCs do not express significant histocompatibility complexes and immune stimulating molecules. Consequently, they escape immune surveillance and their clinical utilization in transplantation is not associated with graft rejection [10].
8 Stem Cell Therapies in Systemic Sclerosis: An Updated Review , Rehab Y Al-Ansari01, Khalid A Al-Anazi2*
Systemic sclerosis systemic is a systemic autoimmune disease that ultimately leads to severe damage and failure of multiple body organs. The disease is associated with significant morbidity and mortality as well as poor response to the available immunosuppressive therapies. Stem cells particularly hematopoietic and mesenchymal stem cells have recently been shown to be not only safe but also efficacious in the treatment of patients with systemic sclerosis. Autologous transplantation of hematopoietic stem cells has become the standard of care for patients with severe systemic sclerosis. Mesenchymal stem cells, alone or in combination with other therapies, have been shown to be effective in the treatment of certain forms and complications of systemic sclerosis such as chronic sclerodermatous graft versus host disease. The review will discuss the various aspects of systemic sclerosis and it will highlight the role of hematopoietic as well as mesenchymal stem cells in the treatment of systemic sclerosis.
9 Donor Selection is a Critical Component Using Naïve Endogenous Adult Stem Cells for the Treatment of Chronic Diseases and Traumatic Injuries , Henry E Young1-3*, Mark O Speight4-6
Naïve adult endogenous stem cell transplants have been used as a substitute for embryonic stem cells and/or induced pluripotent stem cells for treating individuals with autoimmune, cardiovascular, neurological, orthopedic, pulmonary, renal and systemic chronic diseases and traumatic injuries. This is primarily due to the absence of moral and ethical issues, absence of teratoma formation when transplanting stem cells in the naïve state, readily available populations of stem cells and ease of stem cell isolation for transplant. While a majority of the ongoing clinical trials utilize autologous naive adult endogenous stem cells for treating the individual with their own stem cells, other trials have utilized similar types of allogenic stem cells from donors for the treatment of chronic diseases. For allogeneic naïve endogenous adult stem cells to be utilized for transplant, the donor stem cells should be screened to prevent the potential for Graft Versus Host Disease (GvHD) response where the recipient may destroy the graft or the graft may destroy the recipient; to prevent inoculation of new infectious diseases into the recipient and to prevent transplantation of stem cells with deleterious gene mutations into the recipient. This paper describes the various types of adult telomerase negative and telomerase positive endogenous stem cells being used for transplantation therapies, disease entities they have treated, whether treatments utilized autologous and/or allogeneic stem cells, reported outcomes and proposed selection criteria used in the future for allogeneic adult endogenous stem cells in regenerative medicine.
10 Telomerase-Positive Stem Cells in Adult Porcine and Adult Rat Spleens I. Totipotent Stem Cells , Henry E Young1-3*, Ioannis Jason Limnios4, Frank Lochner5, George McCommon6
Previous studies have reported the presence of endogenous undifferentiated totipotent stem cells within the organs and tissues of various animal species, including the spleen. Since one major function of the spleen is to filter out damaged red blood cells, we wanted to ascertain whether totipotent stem cells existed as a potentially transient circulating population solely within the vasculature and sinusoids of the spleen or whether they existed as an endogenous resident population of primitive stem cells throughout the tissues of the spleen, and potentially involved in the repair of the spleen. The spleens from two separate mammalian species were examined, i.e., adult pigs and adult rats. Adult pigs were euthanized following the guidelines of Fort Valley State University’s IACUC.  Adult rats were euthanized following the guidelines of Mercer University School of Medicine’s IACUC. The spleens were harvested, fixed, frozen, cryosectioned, and stained with an antibody diagnostic for the endogenous totipotent stem cells, i.e., Carcinoembryonic Antigen-Cell Adhesion Molecule-1 (CEA-CAM-1). CEA-CAM-1 positive stem cells were located within the capsule of the spleen, along the splenic trabeculae, within the red pulp, within the white pulp, along the central arteries and surrounding the penicillar arteries of the spleen in both the adult pig and in the adult rat. These results suggested that the totipotent stem cells are a resident population of stem cells within the splenic tissues. Studies are ongoing to address their functional significance in repair of the spleen.
11 Utilizing Adipose Tissue-Derived Stem Cell Strategies for Obtaining Regeneration of Respiratory Tract Fistulas-A Systematic Review , Kulvinder Kochar Kaur1*, Gautam Allahbadia2, Mandeep Singh3
Fistula of the respiratory tract represent an aberrant communication or passage among the respiratory system as well as the digestive tract or the nearby organs. They might originate congenitally or more commonly, iatrogenic with a heterogeneous presenting features. These fistulas of the respiratory tract might cause decreased health-associated Quality of Life (QOL) as well as short lifespan. Treatment is basically dependent on an endoscopic surgical procedure but mostly patients need continued hospitalization as well as might develop complications. Thus with the advent of stem cells, the more conservative strategies utilizing regenerative medicine strategies basically dependent on lipotransfer, have been evaluated. After having reviewed the role of Adipose Tissue-Obtained Stem/Stromal Cells (ASC’S) in various kinds of regenerative medicine, here we tried to conduct a systematic review on ASC. Adipose Tissue (AT) might be administered in the form of unprocessed tissue or subsequent to enzymatic treatment to be able to obtain the cellular Stromal Vascular Fraction (SVF).Thus here we conducted a systematic review on the same. With role of stem cells be it Mesenchymal Stem/Stromal Cells (MSCs) or Adipose tissue-derived stem/ stromal cells (ASC’S) in the repair of respiratory tract fistulas. Utilizing the Pubmed search Engine, along with Google Scholar ,Web of Science Scopus, Clinicaltrials.gov for clinical trials utilizing MeSH terms like Bronchopleural Fistula (BPF); to Tracheooesophageal Fistula (TEF); Mesenchymal Stem Cells (MSCs); Mesenchymal stromal cells; Adipose tissue-derived Stem/ Stromal Cells (ASC’S); respiratory tract fistulas; post cancer head and neck fistulas; lipoaspirate from 1960-2020 till date . We found a total of 175 articles out of which we selected 110 articles for this review. No meta-analysis was done. With minimal clinical experience maximum of which comes from case reports as well as case studies, a total concluding proof is still not there. But definitely it is a gradually evolving field with more experience gained, grafting of adipose tissue obtained stem/stromal cells might turn out to me the least invasive as well as more conservative therapy alternative towards the more mutilating damaging extensive surgeries. The safety as well as tolerance observed in earlier studies might aid in strategizing as well as designing larger designs in future which might utilize novel methods with regards to tissue processing along with utilization of scaffolds as well as awa 3D printing in the longer plans for enhancing the clinical results.
12 Longitudinal Assessment of FEV1 Change Following Autologous Cellular Therapy , Melissa M Rubio1*
Objective: Current pharmacologic management of Chronic Obstructive Pulmonary Disease (COPD) is aimed at improving symptoms and preventing exacerbations, yet none can alter the natural progression of lung function decline typical of the disease. Autologous-derived PRP-PC may prevent lung function decline and improve quality of life. Methods: 281 patients with COPD underwent autologous cellular therapy with PRP-PC. Baseline lung function and quality of life data were collected and re-assessed after 3 months and after at least 12 months and compared to baseline. Results: Participants undergoing autologous cellular therapy with PRP-PC had a and clinically significant increase in lung function after both 3 months and after at least one year with along with a significant improvement in subjective quality of life from baseline. Compared with findings in the literature that FEV1 typically declines over time, participants in this study had a significant increase in lung function on average. Conclusion: Innovative treatments such as autologous cellular therapy can be a safe, effective option for preventing lung function decline over time. These therapies should be an option for patients where pharmacologic management has failed, or as an adjunct treatment.
13 Telomerase Positive Totipotent Stem Cells and Pluripotent Stem Cells in the Adult Brain I. Cerebral Cortex , Henry E Young1-3*, Frank Lochner1,4
Previous isolation studies noted the presence of native undifferentiated telomerase positive stem cells within the brains of adult rats. Further segregation of the cells from the brain isolates demonstrated the presence of telomerase positive totipotent stem cells and pluripotent stem cells within the cell isolates. Characterization studies of their differentiation potential noted that both the telomerase positive totipotent stem cells and pluripotent stem cells would form neurons, ganglion cells and glial cells, as well as cells from surface ectoderm, mesodermal and endodermal embryonic germ layer lineages. Since reports from other groups noted the presence of neural stem cells within the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus, we wanted to ascertain the locations of these native telomerase positive totipotent stem cells and pluripotent stem cells within various regions of the adult brain. The brains from adult rats were examined. Adult rats were euthanized following the guidelines of Mercer University School of Medicine’s IACUC. The rats were perfused with ELICA fixative, the brains harvested, frozen, cryosectioned and stained with antibodies diagnostic for the endogenous totipotent stem cells, i.e., carcinoembryonic antigen-cell adhesion moleculae-1 (CEA-CAM-1) and pluripotent stem cells, i.e., stage-specific embryonic antigen-4 (SSEA-4). Both CEA-CAM-1 and SSEA-4 positive stem cells were located within the gray matter of the cerebral cortex, whereas SSEA-4 positive cells were also located in the white matter. These results suggest that the totipotent stem cells and pluripotent stem cells are a resident population of stem cells within the cerebral cortex of the adult brain. Studies are ongoing to address their functional significance in the brain.
14 The Jounced Entrails-Intestine in COVID-19 , Anubha Bajaj1*
Coronavirus disease 2019 (COVID-19), initiated by contemporary coronavirus is a pandemic which engenders severe respiratory disease. SARS-CoV-2 preponderantly transmits through airborne particles and mammoth respiratory droplets additionally, gastrointestinal symptoms are manifested as anorexia, diarrhoea, vomiting, nausea, abdominal pain, hepatic involvement and gastrointestinal haemorrhage. SARS-CoV-2 employs receptors for Transmembrane Protease Serine 2 (TMRPSS2) in order to infect cells in order to engender modifications of Angiotensin Converting Enzyme II (ACE2) within the gut which enhances probability of intestinal inflammation and diarrhoea. Comorbidities such as asthma, hypertension, smoking, Alzheimer’s disease, dementia or disease occurrence in male subjects are associated with disease severity, concurrent complications and mortality in COVID-19.
15 Platelet Rich Plasma- Platelet Concentrate Therapy in COPD: An Observational Cohort Study , Melissa M Rubio1*
Objective: Current management of Chronic Obstructive Pulmonary Disease (COPD) is aimed at improving symptoms and preventing exacerbations, yet those treatments cannot alter the natural progression of lung function decline over time.  Autologous cellular therapy with PRP-PC may help prevent decline and improve quality of life among these patients. Methods: 419 participants with COPD enrolled in this study underwent autologous cellular therapy with PRP-PC and outcomes measures assessed over the course of a year. Lung function with spirometry and breathing-related quality of life was assessed on all patients at baseline.  Quality of life was re-assessed on all participants after 3, 6 and 12 months by phone and 150 participants returned for repeat spirometry after 3 months. Safety monitoring was done on all participants during the study. Results: Participants with COPD, undergoing autologous cellular therapy with PRP-PC, had a statistically significant increase in FEV1% predicted at 3 months post-treatment. In addition, they had a statistically and clinically significant increase in subjective quality of life at 3-, 6-months and 12 months post-treatment.  Adverse events were rare and minor and largely related to the process of drawing blood. Conclusion: Advanced treatments such as autologous cellular therapy with PRP-PC can be a safe, effective option for helping to mitigate the natural progression of COPD.  This study and others published in the literature have found significant improvements in pulmonary function and quality of life when autologous PRP-PC is used. Current pharmacologic therapies are aimed at relieving symptoms and preventing acute exacerbations, but cellular therapy may alter the progressive decline of chronic lung disease over time. Cellular therapies should be considered as a safe, valuable, potential therapy for these patients. An additional comparative, randomized, double blind study comparing this PRP-PC protocol plus standard of care versus standard of care alone is being planned.
16 Expression of Neuron Specific Neuronal Nuclei Protein (NeuNNP) by AAV2 Shows Diagnosis Ability in Spinal Cord Injury Using Neural Stem Cells , Prithiv Kumar KR1,2*, Albert Alukkal3,4
Fibroblast Growth Factor (FGF) shows promising therapy for Spinal Cord Injury (SCI). Neural stem transplantation has been on the role implementing tactics to repair SCI. Considering the hostile hypoxia condition in SCI, Adeno Associated Virus 2 (AAV2) a prototype to AAV is being used for most trials. Basic FGF gene was used in that hostile environment, results showed improved functional recovery in SCI. The regulation of this gene FGF is transduce to yield AAV2-5HRE-bFGF. The improved scores on inclined plane test of BBB (Basso-Bettie- Bresnahan) scale and footprint analysis of functional recovery when compared with vehicle control of AAV2 treatment showed inclination in NeuNNP, neuromodelin GAP43 and neurofilament NF200 and declination in Glial Fibrillary Acidic Protein (GFAP). Other expressions such as LC3-II and Beclin 1 and autophagy-associated proteins all show decline, P62 protein is the oynone that has increased in AAV2 treatment group. This is the key to future treatments of the expression in SCI.
17 A Porcine Model for Repair of Long Bone Non-Union Defects Using Three-Dimensionally Printed Scaffolds , Derek J Milner1†, Sierra A Long1†, Colleen L Flanagan2, Scott J Hollister3, Robert Gurtler1,4, Robert Bane1,4, Jerrad Zimmerman1,4, Jo Ann Cameron1, Santiago D Gutierrez-Nibeyro1, Matthew B Wheeler1*
Background: Approximately 5-10% of bone injuries in the United States result in non-union, costing an estimated $10.4-26.1 billion annually for treatment. While several orthopedic strategies to address non-unions in long bones are available, all have drawbacks and risks of complications. A possible alternative is the recent advances in tissue engineering treatments that are improvements over current treatment options. Methods and Findings: We have developed a porcine long bone segmental defect model for testing osseous non-union repair using 3D-printed biodegradable scaffolds. We generated a 3.5 cm mid-diaphyseal defect in the right radius of a six-month-old pig. A Polycaprolactone (PCL) scaffold implant designed from radius Computed Tomography (CT) scans and produced using solid form fabrication was implanted into the defect and stabilized with a stainless-steel plate.  The animal could stand and place weight on the limb at six hours post-surgery and ambulating without a noticeable limp by four weeks. CT imaging post-surgery show bone fill in the defect space by two weeks, significant defect closure by eight weeks and complete union by 24 weeks. This healing has taken place on a PCL scaffold with no other treatments in conjunction with the implant. Conclusion: The porcine radius segmental defect model provides a viable platform for testing printed scaffolds and bioengineered composite scaffold constructs for the efficacy of healing segmental defects and other forms of non-union in long bones.
18 Unprecedented Year Story to Success , Prof. Laila M Montaser1*
I was thinking of finding what I would discuss in a 2 page new Editorial as I have several matters to say and then destiny made it easy by suddenly receiving three invitations to be nominated for three global awards. So, I have emphasized to write this paper highlighting the story from the start behind these invitations. This is the most recent upshot presage of success I gained after a one year journey from the fighting of COVID-19 pandemic by my unmatched notion to warfare the virus during the world shutdown and staying at home by acting from my home desk [1]. The three global awards are: two from an esteemed American Global Association for the Advancement of Science; the first one honor scientists whose exemplary actions have demonstrated scientific responsibility in challenging circumstances, while the second awards scientists whose ideal work have proved advancement of science. The announcement about the third prize I received was from an Italian respected World Academy of Science will be awarded in recognition of scientists who have made significant contributions to popularize science and have developed new strategies that serve the popularization of science and technology in developing countries. Thanks to awards organizers for selecting and inviting me to nominate for these honorable prizes in this particular time which indicate their awareness and following my continuous efforts in offering significant and innovative contributions to popularize science, development of scientific thought, to the application of science and technology to industry and to human well-being, doing to save the public health integrity and wellbeing of people and presenting an exceptionally model in holding out the duties of scientists in braving situations as happened during COVID-19 crisis.
19 Jejunal Atresia with Hirschsprung’s Disease: A Case Report , Michinobu Ohno1*, Miwako Nakano1, Endo Masao1, Fumiko Yoshida1, Rie Irie1
A rare case of congenital intestinal atresia associated with Hirschsprung disease was?reported. A 0-day-old boy who was diagnosed to have intestinal atresia and he underwent intestinal anastomosis. The movement of the intestinal tract was slow after surgery. The abdominal distension is getting stronger. The radiograph and contrast enema revealed the possibility of Hirschsprung disease. The biopsy of rectum also revealed aganglionosis. Transverse colostomy was performed on the 145th days after surgery of ileal atresia. The radical surgery for laparotomy-assisted trans anal pull-through technique was performed on the 376th days after first surgery. Discussion was made as to its pathogenesis and timing of surgery.
20 After Effects of COVID-19 and Repair of Lungs , Prithiv Kumar KR1*
Lung disease is the most effected organ in patients. Corona (CoV) targets the lungs and causes death of millions of patients across the globe. There has been increasing burden in lung associated disease due to the pandemic. CoV is a deadly pandemic that cause respiratory problems and affects trachea of lungs. CoV which enters the respiratory system, where enzyme is present, and destroy the respiratory organ, causing patients to face difficulty in breathing. There are two steps basically for virus to infect lungs. First pathogenesis converting enzyme to its protein, second cellular protease letting virus through respiratory system. The spike activates into membrane and releases the virus RNA. The present target for the virus is to infect the lungs, while T and B lymphocytes is always negative in ACE2. So proposed solution is stem cell treatment. The release of cytokines S1, S2 and RBD results in edena dysfunction of acute respiratory collapse and cardiac arrest.
21 Adipose-Derived Stem Migration in the Vascular System after Transplantation and the Potential Colonization of Ectopic Sites in Swine , Shanna M Wilson1, Michael S Goldwasser1, Sherrie G Clark1, Elisa Monaco1, Sandra Rodriguez-Zas1, Walter L Hurley1, Matthew B Wheeler1*
Background: Adipose-derived Stem Cells (ASC) are obtained from adipose tissue. They can be harvested by liposuction under local anesthesia, making these cells particularly desirable for use in tissue engineering or cell transplantation. However, little is known about the in-vivo characteristics of these cells post-transplantation. Methods and Findings: Here we evaluate the potential of ASC to migrate systemically and the potential for accumulation and colonization in ectopic tissues in a pig model. ASC injected via ear vein can travel through the entire vasculature of the pig within 60 seconds and the cells continue to be present in the bloodstream for at least 1-hour post- transplantation. However, labeled cells were not present in the bloodstream at 2 or 4 weeks after ASC injection. The injected ASC appear to travel to areas of induced trauma and are not observed in filtering tissues of the body such as the spleen, liver, lung and liver. Conclusion: These findings suggest that systemic administration of ASC could be a successful method of cell transplantation for tissue regeneration.
22 Non-surgical Jowl and Jawline Rejuvenation with Resorbable Suspension Threads and Superficial Enhanced Fluid Fat Injection (SEFFI) , Mattia Colli1*, Alessandro Gennai2, Rosalba Russo3, Andrea Tomeo4, Bruno Bovani5, Domenico Piccolo6, Fabrizio Melfa7, Piero Tesauro8, Alberto Diaspro9
Background: Collagen and elastin play a crucial role in skin traction; their deterioration contributes to causing skin sagging and laxity with time. Soft tissue ptosis modifies the mandibular profile in addition to enhancing the nasolabial folds, lines of puppets and lateral eyebrow area; moreover, skin atrophy and volume loss are major factors involved in facial aging, contributing to the formation of facial rhytids, skeletonization, and pseudo-descent of the midface. Non-surgical face and neck rejuvenation lift with resorbable suspension threads and Superficial Enhanced Fluid Fat Injection (SEFFI) can be used as a temporary procedure until the aging appearance requires a more radical approach. Methods: Retrospective analysis from January 2019 to February 2022 of a 232 cases series of patients seeking a rejuvenation of the lower frame of the face (jowls and jawline) included in the study. The cases were performed in the base-office medical suites of some of the Authors. All of them were treated with resorbable threads in the face subcutis without modifying the superficial musculoaponeurotic system and platysma. Result: Data collection on base-office medical suites treatment time, size and length selection, and post- treatment complications were included. The most frequent complication was bruise in the harvesting area (healed within 3-7 days) and in the jowl and jawline; cases of skin irregularities in threads (all cases solved 7-10 days); no skin irregularities or lumpiness in tissue graft. Conclusion: Non-surgical face and neck treatment with resorbable suspension threads and Superficial Enhanced Fluid Fat Injection (SEFFI) getting a valid method as a temporary procedure until the aging appearance requires a more radical approach.
23 Preparation of Nanofat Concentrate and Its Use for Hypertrophic Scar Treatment , Sheng-Hong Li1, Yin-Di Wu1, Ze-Hua Li1, Xiao Jiang1, Xuan Liao1, Guang-Hui Xie1, Li-Ling Xiao1, Ting Wan2, Hai-Ling Huang1, Hong-Wei Liu1*
Objective: Nanofat grafting has been reported to improve tissue repair by the Stromal Vascular Fraction (SVF) of nanofat. However, the oil and liquid portions of fat tissues were released by mechanical emulsification during the nanofat procedure. Here, we reported a simple method to remove the oil and water for concentrating nanofat. Methods: The concentrate of nanofat was obtained by processing nanofat using negative pressure produced by syringer and two-step centrifugation. The volume of oil and fat tissue as well as morphological changes of nanofat concetrate obtained by different procedures was examined. Meanwhile, the SVF numbers, the proliferation and differentiation capacity of Adipose-Derived Stem Cells (ADSCs) were determined. The clinical outcome of nanofat concentrate in treatment hypertrophic scar was evaluated. Results: The centrifugation and negative pressure had no significant effect on the proliferation activity of the SVF in the concentrate of nanofat. The concentrated rate after 0, 15, 30 and 60 times of emulsification was 2.08±0.042, 2.63 ± 0.07, 3.8 ± 0.01 and 8.2 ± 0.12 times greater than the original, respectively. The SVF number per 10 ml of fat in the above-mentioned groups were increased by 1.80 ± 0.15, 2.68 ± 0.27, 4.64 ± 0.20 and 3.44 ± 0.27 times, respectively. The capacity of cell proliferation and differentiation decreased significantly after more than 30 times emulsification. The concentrates of nanofat effectively improve the appearence and hardness of hypertrophic scar. Conclusion: The nanofat concentrate prepared by our method include more SVF cells and less oil and might be more effective during clinical use.
24 3D Bioprinting for Tissue Engineering Amidst the Century Cataclysm, Laila M Montaser1*
The coronavirus is one of our modernistic day’s major universal, human defies. The human brain is planned to prefer the present-day and underrate the future. That triggers it hard to prohibit disasters like pandemics. Numerals of medications are presently under examination for the therapy of COVID-19 illness. Whilst these remedies can ameliorate a patient’s recuperation and existence, these curative methods do not achieve frank repair of the lung injury stroked by this sickness. Stem cell therapies are prominent as novel favorable remedies, which could decline inflammation but as well rejuvenate the lung harm caused by COVID-19. Stem cells extend their immunomodulatory, anti-oxidant and reparative curative impacts that could be useful, single or incorporation with other medicinal factors, in patients with COVID-19. Stem cells can be used to outline this hurt by using their renovated characteristics, which allows them to prospect promoted clinical usefulness contracted to else scrutinize pharmacological therapies. Modern proceeds in regenerative medicine have affirmed the chance to generate applicable and active tissue engineering 3D erects containing spirited cells for tissue reform and increase. 3D bioprinting has protruded as a hopeful novel tactic for making compound biological rears in the domain of tissue engineering and regenerative medicine. It targets to lessen the hurdles of imitative tissue engineering procedures by exact and planned layer-by-layer congregation of biomaterials in a required 3D modality. Cell printing aims to transport energetic cells in a 3D style to represent stem cell niches and pathological tissue morphologies for drug examination, or to imitate human tissue confusion acting as biologically pertinent subrogates. A pliable 3D tissue engineering technology authorizes stem cells created from a person’s possess body to split after printing and distinguish in a track to compose and substitute any tissue kind of the body. 3D printing technicalities can distinguish stem cells into lung cells. 3D printing can be utilized to overcome the individual defensive tool lack caused by the new COVID-19 and likewise to employ the technology to originate specimens of human organs and tissues for trials objectives.
25 Human CO Model of Creutzfeldt - Jakob Disease (CJD) Evaluates the Effect of Putative Drugs on Prion Accumulation, Prithiv Kumar KR1*
Creutzfeldt Jakob Disease (CJD) is incurable and fatal neurodegenerative disease. The treatment in human is cell based models for prion disease. An induced pluripotent stem cell based models of human cerebral organ has shown to cure CJD prions. This model has new screening methodology for drug induced candidates in certain genetic background. Using anti-prion disease, first ever model was screened for drug induced patients. Pentason polysulfate delayed methodology along with prophylactic has been a remedy for treatment. These are the first regenerative treatment that can concur results for CJD.
26 A Regenerative Interventional Approach to the Management of Degenerative Low Back Pain, Edilson Silva Machado1*, Fabiano Pasqualotto Soares1, José Manuel Peixoto Caldas2
Objective: Low back pain has been strongly related to the degenerative process of the spine, especially the degeneration of the intervertebral disc and facet joints. The main procedures for the management of low back pain are no intended to slow down or reverse the degenerative process. Platelet Rich Plasma (PRP), an orthobiologic product, has been the subject of several studies in the management of low back pain. Methods: A prospective case series study presenting the clinical results of 23 patients treated with PRP injections performed following clinical a interventionist protocol called PerMuTIS – Personalized Multi Target Biologic Injection of the Spine. The method to obtain the platelet concentrate was the Simple Double Spin technique, a low-cost double spin that produces Leucocyte Rich PRP. Baseline scores of pain and disability using the Visual Analog Scale (VAS) and Roland-Morris Disability Questionnaire (RMDQ) were recorded. Results: Mean VAS pain score across the cohort decreased by approximately 62%, while the Roland-Morris disability score decreased by about 60% at 52 weeks. There was no report of adverse events. The Leucocite and Monocite Rich PRP product showed concentration of 4.3X above baseline, with monocites concentration of 3.2X baseline. Conclusion: The concept of application in multiple targets using a simple and low-cost preparation technique proved to be feasible and without reports of serious side effects that compromise its indication. The PerMuTIS – Personalized Multi Target Biologic Injection in the Spine Technique using Simple Double Spin protocol demonstrated safety and feasibility in this prospective study of patients with low back pain who failed conservative treatments. Large scale, multicenter randomized clinical trial will provide an appropriate level of evidence to assist in clinical practice.
27 The Use of Stem Cell-Derived Organoids in Cancer Treatment Research , Amanda Geissler1, Vincent S Gaillicchio1*
Cancer is one of the leading causes of death worldwide. While some forms of cancer are more manageable and nonfatal with treatments like chemotherapy and radiation, other forms are not as manageable and have high fatality rates, such as colorectal cancer. Colorectal cancer most commonly occurs in elderly adults but has the potential to occur at any age. Due to its sometimes-undetectable symptoms, it is often diagnosed at a very late stage. Once diagnosed, there are different levels of treatment. For example, surgical resection, chemotherapy, radiation, or any combination of the three can occur. When tumors are unresectable, patients are often left with little chance of survival, and receive only the extension of survival for a short period of time. While surgical resection, chemotherapy and radiation have had success in some patients, high recurrence rates and a lack of response to treatments have left patients and researchers looking for new treatments that will result in better survival rates for patients. Researchers have begun to answer the calls for new treatments with the discovery of patient-derived organoids. Patient-derived organoids are harvested from adult stem cells in the desired tissue, or from cancer cells in a patient’s tumor. The cells taken from the patient are then grown ex-vivo in conditions that mimic the inside of the body. Organoids have grown to show both structural and physiological similarities to their parent organ. While organoids have not yet grown to be as large and highly vascularized as their parent organ, they have been useful in disease modeling and drug therapy testing. Patient-derived organoids that have been grown ex-vivo have shown to overlap almost completely with their parent organ in terms of genetic sequence and molecular makeup. Due to their high number of genetic similarities, patient-derived organoids have been shown to react the same way to certain drug treatments in a few studies, which allows researchers to provide combinations of different cancer drug treatments that are tailored to each individual patient, rather than using a standardized approach that only seems to work for some patients. Patient-derived organoids are still a rather new approach to cancer drug therapy testing, and they still present some limitations, such as their inability to grow as large and as highly vascularized as their parent organ. While these limitations may have the ability to hinder the effectiveness of patient-derived organoids, some organoids have shown success in colorectal cancer drug therapy trials, and their limitations are likely to be overcome as more information is known about patient-derived organoids. Organoids are a promising approach to the treatment of colorectal cancer and have the potential to help save more patients than previous approaches.
28 Ocular Damage in Craniofacial-Orbital Trauma: About 170 Cases The Comorbidity of Alzheimer’s Disease and Bipolar Disorder and the Potential of Lithium as Drug Therapy , Samantha Albano1, Vincent S. Gallicchio1*
Bipolar disorder is characterized by having pathological fluctuations in mood and energy that result in severe psychological issues and an increased risk of suicide. More than 4% of the adult population is affected by this disorder and as a result is at a higher risk of developing certain neurodegenerative disorders, such as Alzheimer’s disease. Alzheimer’s disease affects more than 6.2 million Americans over the age of 65 and is currently the sixth leading cause of death in the United States. There is currently no approved therapeutic approach to treat Alzheimer’s disease, however, the comorbidity of bipolar and Alzheimer’s disease has encouraged the investigation of lithium as a possible method of treatment. Lithium has been used to treat bipolar disorder for years and has recently been shown to increase gray matter density in the brain as well as encourage stem cell proliferation in areas where cell dysfunction and death have occurred. Research has shown chronic lithium usage can decrease the rate that dementia develops in high-risk individuals, such as individuals with bipolar disorder.
29 The Effect and Mechanism of Lithium Carbonate on Bipolar Disorder and its Immunological Contributions , Megha Gupta1, Vincent S Gallicchio1*
Bipolar disorder is a mental disorder that affects hundreds of thousands of people worldwide. Common treatment options are cognitive, behavioral, and medicinal treatment, though medicinal treatment is shown to be most effective because the brain is shown to be “damaged.” This damage is evidence based on a significant reduction of gray matter in neural areas that enable and/or regulate bipolar-related symptoms. This is evident in immunological-related responses against the brain during a brain trauma or stroke, and similar clinical values are observed during episodes of psychosis, leading researchers to believe that drug treatment is beneficial to treat the misrepresented neurodegenerative disease. Lithium carbonate is a drug commonly used to treat bipolarism as it is proven to reduce the effects of mania and psychosis as well as serve to be prophylactic against episodes of depression. It is also shown to elevate levels of white blood cells through its influence on signaling pathways within the brain that encourage an increased granulocyte production. Though, as beneficial as it is to treat bipolar-related symptoms and potentially increase the immunological response within the body, its toxicity is quite dangerous in harmful amounts. Current research is now moving forward to continue the investigation of lithium on white blood cells.
30 A Gout Flare Caused by the Administration of Platelet Rich Plasma: A Clinical Case, Plamen Todorov1*, Anastas Batalov1
The therapy with Platelet Rich Plasma (PRP) administered in degenerated or injured musculoskeletal tissues is a new and promising regenerative treatment option. Traditionally, it is considered that as PRP represents an autologous (to the patient) blood product, the potential for serious side effects is neglectable. Consequently, it is important that any significant negative consequences are well described. We present a fifty-five years old male patient, complaining of pain and stiffness in his right ankle joint due to multiple traumas during his earlier sport career. He had no any contraindications and PRP was injected intraarticularly under ultrasound guidance. On the next day, the patient developed an intensive pain and swelling in the regions of the right ankle and the dorsum of the right foot. The acute phase reactants were elevated and there was no leukocytosis. On ultrasound examination, there was an effusion in the tibiotalar and talonavicular joints. Arthrocentesis was performed and the microscopic examination revealed the typical needle shaped monosodium urate crystals inside the joint fluid and no bacteria. Consequently, the diagnosis of acute gouty flare was made (the patient has a history of gout, but did not have any flares in the past two years). As PRP concentrate contains naturally many proinflammatory molecules, we speculate that some of them may activate the macrophages that residue normally in the synovium and the capsule of the injected joint. The activated macrophages further may react to the MSU crystals deposited there, leading to the development of a gouty flare. In conclusion, the possibility of a flare should be explained to gouty patients, candidate for PRP treatment.
31 Repair of Bowel Perforation: Endoscopic State of the Art, Ashkhan Hojati1, Joseph Policarpio1, Matthew B Wheeler1*, Blair Rowitz1
Background: Intestinal damage from various etiologies can result in the potentially dangerous complication of bowel perforation. Emergent treatment of small bowel perforation includes surgical repair with or without small bowel resection. As the number of therapeutic and diagnostic endoscopic procedures increase, more studies may be required to properly evaluate and report incidences of bowel perforation. Given the advantages of interventional procedures, novel endoscopic technologies which may prove beneficial in bowel perforation repair are continuously undergoing development. Bowel perforation can lead to peritonitis and sepsis – a medical emergency requiring immediate attention. Following diagnosis, hemodynamically stable patients may be treated conservatively whereas unstable patients undergo more intensive surgical procedures. Endoscopic procedures for bowel perforation repair also exist and recent advances in technology are furthering the scope of such closure methods. Methods and Findings: Endoscopic suturing technologies, while capable, require extensive training and entail prolonged activation processes. Wound vacuum sponge closure via endoscopy provides convergence of wound defects but may not be efficacious in defects larger than 5 cm. Furthermore, this method may be limited by inadequate seal and placement in the intestine. Endoscopic clipping is another modality beneficial for smaller perforations only. T-tag suturing has shown promising results in ex-vivo studies but entails blind placement of T-tags for perforation closure. Stents can be inserted endoscopically under fluoroscopic visual guidance. This technique, however, may result in stent migration, perforations and potential occlusions. Sealants can be injected for perforation closure but have not demonstrated clear efficacy. Robotic flexible endoscopy provides several novel features yet may require advanced training and sometimes more than one operator. As interventional procedures continue to gain popularity, a better understanding of endoscopic modalities is helpful for furthering their development. Regarding bowel perforation, this review aids in an overall understanding of the technologies which exist and are advancing further into more standard modalities for practical medical applications. Conclusion: There are currently various methods to repair perforation of the gastrointestinal wall and except for urgent exploratory laparotomy when indicated, there is likely no single method that is superior to others. It may be beneficial for the physician to consider all options for repair when evaluating a potential bowel perforation, considering physician preference and individual success or difficulty with a given modality. In more recent years as the focus has narrowed on minimally invasive procedures, future modalities will likely include increased automation and ease of use with the help of robotics, which will hopefully lead to decreased time to diagnosis, faster recovery and reduced morbidity and mortality.