Interrogating erectile dysfunction and evaluating novel therapeutic frontiers, with emphasis on stem cell strategies.

Male infertility arises from a complex interplay of factors affecting reproductive organs and various physiological pathways. Among these, erectile dysfunction (ED), a widespread global issue, plays a key role. While existing ED treatments address some aspects, achieving complete reversibility and avoiding side effects remains a challenge. In this context, stem cell therapy emerges as a promising, potentially transformative approach. Preliminary evidence from preclinical animal models and clinical trials highlights stem cell therapy's remarkable efficacy and effectiveness for ED. This novel strategy offers several advantages, including enhanced effectiveness and a reported absence of adverse side effects. This review delves into the causes of male infertility, with a particular focus on ED and its pathophysiology. We explore the current treatment landscape, highlighting therapy's existing strategies' limitations and stem cell therapy's unique potential. By examining relevant preclinical and clinical studies, we provide a comprehensive picture of this innovative approach and its promising future in restoring men's fertility and quality of life.

From stem cells to extracellular vesicles: a new horizon in tissue engineering and regenerative medicine.

In the fields of tissue engineering and regenerative medicine, extracellular vesicles (EVs) have become viable therapeutic tools. EVs produced from stem cells promote tissue healing by regulating the immune system, enhancing cell proliferation and aiding remodeling processes. Recently, EV has gained significant attention from researchers due to its ability to treat various diseases. Unlike stem cells, stem cell-derived EVs show lower immunogenicity, are less able to overcome biological barriers, and have a higher safety profile. This makes the use of EVs derived from cell-free stem cells a promising alternative to whole-cell therapy. This review focuses on the biogenesis, isolation, and characterization of EVs and highlights their therapeutic potential for bone fracture healing, wound healing, and neuronal tissue repair and treatment of kidney and intestinal diseases. Additionally, this review discusses the potential of EVs for the treatment of cancer, COVID-19, and HIV. In summary, the use of EVs derived from stem cells offers a new horizon for applications in tissue engineering and regenerative medicine.

Primary Gastric Synovial Sarcoma in a Young Male: a Rare Case Report and Review of Literature.

We are reporting a rare case of primary gastric synovial sarcoma in a young male. Synovial sarcoma of the stomach is a very rare tumor. The common involved sites of occurrence of synovial sarcomas are upper and lower extremities. In the English literature, only 47 cases of primary synovial sarcoma of stomach have been reported. Spindle-shaped tumor cells are the basic content of synovial sarcomas with varying degrees of epithelial differentiation. The basic classification of synovial sarcoma depends on the histological pattern and the degree of differentiation and it is classified as monophasic, biphasic, and poorly differentiated. Synovial sarcoma presents with classical chromosomal translocation where they form fusion genes of SS18-SSX1, SS18-SSX2, and SS18-SSX4. Fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR) are the molecular analysis techniques to detect these fusion genes. As the available literature support is limited, the role of adjuvant chemotherapy, radiation therapy, and intra-operative lymphadenectomy is still unclear. However, surgical resection with clear margin is the gold standard treatment.

Modified Radical Mastectomy vs Breast-Conserving Surgery: Current Clinical Practice in Women with Early Stage Breast Cancer at a Corporate Tertiary Cancer Center in India.

Breast cancer is the most common cancer in women in urban India and surgery has one of the definitive roles in treating this cancer. Over the decades, multiple studies have been published and they have shown that BCS followed by radiotherapy has equivalent disease-free survival (DFS) and overall survival (OS) as compared with MRM. The surgeon has the main role in explaining the treatment options to the patient. It is a prospective study conducted at Vedant Cancer and Multispeciality Hospital in a metropolitan city, Thane, India. Patients with stage I or II breast cancer with tumor size less than 5 cm were included in the study. Patients with locally advanced and metastatic breast cancer were excluded from the study. The study population was early breast cancer patients registered and waiting for surgery (n = 86) at Vedant Cancer and Multispeciality Hospital from November 2019 to end of April 2020. The total number of females enrolled in the study were 86 and out of this, 79.1% (n = 68) females opted for MRM and 20.9% (n = 18) females opted for BCS in which 8 patients had changed their decision after re-counseling in the ward from MRM to BCS. The most common reasons selected by patients to undergo MRM were fear of cancer recurrence (30.2%, n = 26), avoidance of side effects of radiation therapy (25.5%, n = 22) and fear of radiation therapy (23.2%, n = 20). Surgeon had decided the surgical option in 79.1% (n = 68) cases. The study shows that the treating surgeon and patient's husband are the principal persons who decide the surgical option and active participation of women during counseling is an important factor. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-021-01457-8.

Convalescent plasma therapy - a silver lining for COVID-19 management?

ABSTRACT The COVID-19 pandemic has pushed the world towards social, economic, and medical challenges. Scientific research in medicine is the only means to overcome novel and complex diseases like COVID-19. To sum up the therapeutic wild-goose chase, many available antivirals and repurposed drugs have failed to show successful clinical evidence in patient recovery, several vaccine candidates are still waiting in the trial pipelines and a few have become available to the common public for administration in record time.However, with upcoming evidence of coronavirus mutations, available vaccines may thrive on the spirit of doubt about efficacy and effectiveness towards these new strains of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV2). In all these collective uncertainties, plasma therapy has shown a ray of hope for critically ill patients. To date, with very few published case studies of convalescent plasma in COVID-19, there are two school of thought process in the scientific community regarding plasma therapy efficiency and this leads to confusion due to the lack of optimal randomized and controlled studies.Without undertaking any robust scientific studies, evidence or caution, accepting any therapy unanimously may cause more harm than good, but with a clearer understanding of SARS-CoV2 immunopathology and drug response, plasma therapy might be the silver lining against COVID-19 for the global community.

Functional Malignant Retroperitoneal Paraganglioma with Liver Metastasis: a Rare Case Report.

Paragangliomas are rare neoplasms. Their specific annual incidence is still unclear. These are rare neuroendocrine tumors which arise from extra-adrenal paraganglioma and they have the ability to secrete catecholamines. Most of them are diagnosed in the 3rd to 5th decades of life with mean age around 47 years. Majority of them are benign; however, malignant tumors with metastatic behavior are very rare. The incidence of malignant paraganglioma is estimated around 93/400 million people. The clinical course of metastatic malignant disease is variable and the reported 5-year survival is around 12-84%. There is no curative treatment option for malignant metastatic paraganglioma. If resectable, both, primary and metastasis should be resected. The only criteria which defines its malignancy is the presence of metastatic spread of chromaffin cells in tissues that normally do not contain such cells. Functional paraganglioma secretes excessive catecholamines which clinically manifest as paroxysmal hypertension, headache, sweating, and palpitations. We reported a case of young male who presented with huge left retroperitoneal mass and after evaluation found to have a functional malignant paraganglioma with liver metastasis. Surgical resection of the primary malignant paraganglioma with metastatectomy helps in decreasing the complications, improving the symptoms and prolonging the survival.

Convalescent plasma therapy - a silver lining for COVID-19 management?

The COVID-19 pandemic has pushed the world towards social, economic, and medical challenges. Scientific research in medicine is the only means to overcome novel and complex diseases like COVID-19. To sum up the therapeutic wild-goose chase, many available antivirals and repurposed drugs have failed to show successful clinical evidence in patient recovery, several vaccine candidates are still waiting in the trial pipelines and a few have become available to the common public for administration in record time. However, with upcoming evidence of coronavirus mutations, available vaccines may thrive on the spirit of doubt about efficacy and effectiveness towards these new strains of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV2). In all these collective uncertainties, plasma therapy has shown a ray of hope for critically ill patients. To date, with very few published case studies of convalescent plasma in COVID-19, there are two school of thought process in the scientific community regarding plasma therapy efficiency and this leads to confusion due to the lack of optimal randomized and controlled studies. Without undertaking any robust scientific studies, evidence or caution, accepting any therapy unanimously may cause more harm than good, but with a clearer understanding of SARS-CoV2 immunopathology and drug response, plasma therapy might be the silver lining against COVID-19 for the global community.

Immunomodulatory extracellular vesicles: an alternative to cell therapy for COVID-19.

Introduction: SARS-CoV-2 induces a cytokine storm and can cause inflammation, fibrosis and apoptosis in the lungs, leading to acute respiratory distress syndrome (ARDS). ARDS is the leading cause of mortality and morbidity the associated to COVID-19, and the cytokine storm is a prominent etiological factor. Mesenchymal stem cell-derived extracellular vesicles are an alternative therapy for the management of inflammatory and autoimmune conditions due to their immunosuppressive properties. The immunomodulatory and tissue regeneration capabilities of extracellular vesicles may support their application as a prospective therapy for COVID-19.Areas Covered: We explored the clinical evidence on extracellular vesicles as antiviral agents and in mitigating ARDS, and their therapeutic potential in COVID-19.Expert Opinion: Clinical trials using extracellular vesicles are registered against COVID-19 associated complications, with some evidence of safety and efficacy. Extracellular vesicles present an alternative potential for cell therapy for COVID-19 management, but further preclinical and clinical investigations are needed.

Does Preoperative Diagnosis Will Change the Treatment Plan of Clear Cell Carcinoma of Endometrium Masquerading as Desmoid Tumor of Anterior Abdominal Wall?: a Case Report.

Clear cell carcinoma (CCC) of the female genital tract can arise in the ovary, endometrium, cervicovaginal region, in peritoneal and other extra pelvic sites. However, CCC involving anterior abdominal wall is a very rare entity. We are reporting a case of 55-year-old postmenopausal lady with ECOG PS-I with no comorbidity had history of cesarean section about 30 years back and presented with pain in abdomen at periumbilical region about 9 months back. She underwent evaluation at outside clinic with finding of an anterior abdominal wall swelling of size approximately 3 × 3 cm which was completely neglected by the patient. In the next period of 2 months, the swelling suddenly increased in size. CECT/PET CT showed a solid cystic mass involving anterior abdominal wall with possibility of desmoid tumor. We had decided to plan for surgical excision of the tumor. Intraoperatively we found that there was bicornuate uterus. The lesion was arising from one of the cornue of uterus and it was extended anteriorly to anterior abdominal wall with no ascites, no pelvic, or retroperitoneal lymphadenopathy. She underwent hysterectomy with bilateral salpingo-oophorectomy and defect was closed with bioabsorbable mesh. Final histopathology report was clear cell endometrial carcinoma mostly mullerian tract origin arising from endometriosis focus. Tumor cells were diffusely positive for PAX-8 and Napsin-A and negative for WT 1 with patchy positivity for P53 (wild type expression). She had received adjuvant chemotherapy and she is disease free after 2 years of completion of the treatment. Clear cell endometrial carcinoma arising from malignant transformation of an endometriosis focus to anterior abdominal wall is a very rare phenomenon and it is a difficult task to reach its final diagnosis.

Mesenchymal stem cells and exosome therapy for COVID-19: current status and future perspective.

Acute respiratory distress syndrome (ARDS) is the main cause for the COVID-19 infection-related morbidity and mortality. Recent clinical evidences suggest increased level of cytokines and chemokines targeting lung tissue as a prominent etiological factor. The immunomodulatory effect of mesenchymal stem cells (MSCs) as the alternative therapy for the treatment of inflammatory and autoimmune diseases is well known. Several studies have also revealed that similar therapeutic impacts of parent MSCs are also exhibited by MSCs-derived extracellular vesicles (EVs) including exosomes. In this review, we explored the therapeutic potential of both MSCs and exosomes in mitigating the COVID-19 induced cytokine storm as well as promoting the regeneration of alveolar tissue, attributed to the intrinsic cytokines and growth factor present in the secretome. The preliminary studies have demonstrated the safety and efficacy of MSCs and exosomes in mitigating symptoms associated with COVID-19. Thus, they can be used on compassionate basis, owing to their ability to endogenously repair and decrease the inflammatory reactions involved in the morbidity and mortality of COVID-19. However, more preclinical and clinical studies are warranted to understand their mechanism of action and further establish their safety and efficacy.

Gastrectomy with D2 Lymphadenectomy for Carcinoma of the Stomach in a Stand-alone Cancer Centre in Rural India.

CONTEXT: The therapeutic role of D2 lymphadenectomy in the management of gastric cancer is an ongoing controversy. AIMS: To examine the morbidity and oncological outcomes of D2 lymph node dissection for gastric cancer patients treated in a stand-alone cancer center in rural India and to compare it with international data. SETTINGS AND DESIGN: Retrospective study on patients treated for gastric cancer from June 2009 to December 2014. METHODS AND MATERIAL: All patients underwent subtotal or total gastrectomy with modified D2 lymph node dissection preserving spleen and pancreas. The Clavien-Dindo model was used to stratify the severity of morbidity. STATISTICAL ANALYSIS: Descriptive statistics was used for data exploration. Chi-square test was used to compare the association of various factors with survival. Kaplan-Meier method was used to calculate the survival rates (RFS and DFS). Log-rank test was used to compare the survival of different subgroups. RESULTS: Fifty-four patients (41 males and 13 females) were included in the study. Four (7.4%) patients had significant postoperative morbidity. The 5-year OS and DFS respectively were 34.9% and 37.6%. Female sex was associated with poorer survival. Lymph node ratio of more than 0.2 and advanced stage at presentation showed strong tendency towards lower OS and DFS. CONCLUSIONS: An R0 resection with D2 lymphadenectomy for gastric cancer carries acceptable morbidity and mortality in Indian patients with survival rates comparable with the western studies. Lymph node ratio more than 0.2 and female gender and advanced stage were associated with poorer oncological outcomes.

En Bloc Resection with Partial Sacrectomy Helps to Achieve R0 Resection in Locally Advanced Rectal Cancer, Experience from a Tertiary Cancer Center.

Partial sacrectomy is a radical procedure that benefits a select group of patients with locally advanced primary or recurrent rectal cancer with posterior extension and carries potential for significant morbidity. This study was done to evaluate the morbidity and oncological outcome of patients who underwent partial sacral resection for rectal cancer in a tertiary cancer center. Seventeen patients underwent partial sacrectomy during the period from 2011 to 2015. Eleven patients had primary and six had recurrent rectal cancer. All patients were evaluated with MRI pelvis and metastatic evaluation with CT scan of the chest and abdomen and PET scan in patients with recurrent cancer. All patients had resection below the level of S2/S3 junction or lower. Three patients were females and the remaining were males. Median age was 56 years. Overall morbidity was 76% and most common morbidity was wound related. The mean estimated relapse-free survival (RFS) for patients treated for primary rectal cancer was 20.3 months (95% confidence interval (CI), 12.8-27.9) and the mean estimated overall survival (OS) 23.9 months. Estimated mean RFS for patients who were operated for recurrent rectal cancer was 25.6 months (95% CI, 17.7-33.5) and the median RFS was yet to reach. Estimated mean OS was 29.7 months (95% CI, 15.5-43.8) and the median OS was 39.6 months. Partial sacrectomy below the level of S2/S3 junction is a safe approach to facilitate en bloc resection of locally advanced primary and recurrent rectal cancer extending posteriorly with loss of plane with sacrum. In selected patients, this approach can improve survival at the cost of high morbidity.

Functionally coated polyethersulfone hollow fiber membranes: A substrate for enhanced HepG2/C3A functions.

Hollow fiber membrane (HFM) based liver assist systems are a life-saving bridge for patients until a donor organ is available for transplantation or until liver regeneration. However, liver cell attachment and functional maintenance on HFM surface is a major challenge in bio-artificial liver (BAL) support systems. In the present study, novel glutaraldehyde (GTA)-crosslinked gelatin (gel)-coated polyethersulfone (X-gel-PT) HFMs were manufactured using triple orifice spinneret by the dry-wet spinning method. HFMs were characterized for morphology, outer surface roughness, hydrophilicity, tensile strength, thermal stability, BET surface area and pore volume measurements, permeability and rejection. Fourier transform infrared spectroscopy, and transmission electron microscopy confirmed the GTA-crosslinked gel-coating in the X-gel-PT HFMs, which provided the desirable extracellular matrix-like environment to the HepG2/C3A cells. The results of in-vitro hemocompatibility tests showed the better suitability of the developed HFMs for the blood-contact application. X-gel-PT HFMs showed significantly better cellular attachment and proliferation of HepG2/C3A cells on day 3 and 6, as shown by scanning electron and confocal microscopy. Significantly high urea synthesis and albumin secretion seen indicated the improved functional and metabolic activity of HepG2/C3A cells. Thus, the developed X-gel-PT HFMs is a suitable substrate for the hepatocyte culture, mass culture, and development of BAL support system.

Bioinspired Engineering for Liver Tissue Regeneration and Development of Bioartificial Liver: A Review.

Patients with advanced liver disease have very high mortality due to associated complications such as hepatic encephalopathy, hepatorenal syndrome, and multiorgan failure. Liver transplant is the only therapeutic option for such patients; however, problems linked to availability, cost, complications, and side effects limit its practical application. The strong potential for hepatic regeneration and recovery has been documented in liver disease, without advance decomposition of the liver. Recently, hepatocyte transplantation was used as an alternative to liver transplantation, but insufficient numbers of functional hepatocytes for therapeutic efficacy limits its use. In addition, extracorporeal liver support systems are a modality for patient management or they can be used as a bridge to a possible liver transplant. But such systems lack clear-cut survival benefits, specifically in advanced liver disease. Due to the limited amount of organ donations and living donor liver transplantation across the globe, novel technologies have been proposed for development of three-dimensional (3D) composite constructs, 3D perfused bioreactors for spheroid culture, liver-on-chip platforms, and bioprinted liver to produce an implantable in vitro liver that can reliably predict in vivo-like tissue responses and suitability for drug toxicity testing. These research fields stand to be game changers in regeneration and repair of liver tissues in patients. This review focuses on novel technologies that are currently used for liver regeneration and production of transplantable liver.

Islet encapsulated implantable composite hollow fiber membrane based device: A bioartificial pancreas.

Islets from xeno-sources and islet like clusters derived from autologus stem cells have emerged as alternatives to cadaveric pancreas used for treatment of type 1 diabetes. However, the immuno-isolation of these islets from the host immune system suffers from the issue of biocompatibility and hypoxia. To overcome the issues of immunobarrier biocompatibility, we developed a Polysulfone (Psf)/TPGS composite hollow fiber membrane (HFM) using a hollow fiber spinning pilot plant specially developed for this purpose. Important structural variables such as fiber material, dope composition, dimensions, surface characteristics etc., were precisely engineered and tuned for bioartificial pancreas application. The HFMs were characterized for their morphology, molecular diffusion, selectivity and protein absorption. The optimized Polysulfone(Psf)/TPGS composite HFMs, which contained TPGS, exhibited uniformed structure with low insulin adsorption and high permeability of insulin. The HFM was further studied for the encapsulation and in-vitro growth with porcine and differentiated islets isolated from human umbilical cord Wharton's jelly. To prove their efficacy under in-vivo conditions, the Polysulfone(Psf)/TPGS composite HFMs were encapsulated with either of these isolated cells (porcine islets or islet like cell clusters derived from mesenchymal stem cells isolated from human umbilical cord Wharton's jelly) and they were transplanted in experimental STZ induced diabetic mice. The results showed restoration of normoglycemia for 30days, indicating their ability to respond efficiently to high glucose without immune-rejection. Thus, these results indicate that Polysulfone (Psf)/TPGS composite HFMs can be used as an implantable, immune-competent bioartificial pancreas as a therapy for type 1 diabetes.

Artificial Bone via Bone Tissue Engineering: Current Scenario and Challenges.

Bone provides mechanical support, and flexibility to the body as a structural frame work along with mineral storage, homeostasis, and blood pH regulation. The repair and/or replacement of injured or defective bone with healthy bone or bone substitute is a critical problem in orthopedic treatment. Recent advances in tissue engineering have shown promising results in developing bone material capable of substituting the conventional autogenic or allogenic bone transplants. In the present review, we have discussed natural and synthetic scaffold materials such as metal and metal alloys, ceramics, polymers, etc. which are widely being used along with their cellular counterparts such as stem cells in bone tissue engineering with their pros and cons.

Bioconductive 3D nano-composite constructs with tunable elasticity to initiate stem cell growth and induce bone mineralization.

Bioactive 3D composites play an important role in advanced biomaterial design to provide molecular coupling and improve integrity with the cellular environment of the native bone. In the present study, a hybrid lyophilized polymer composite blend of anionic charged sodium salt of carboxymethyl chitin and gelatin (CMChNa-GEL) reinforced with nano-rod agglomerated hydroxyapatite (nHA) has been developed with enhanced biocompatibility and tunable elasticity. The scaffolds have an open, uniform and interconnected porous structure with an average pore diameter of 157±30µm and 89.47+0.03% with four dimensional X-ray. The aspect ratio of ellipsoidal pores decrease from 4.4 to 1.2 with increase in gelatin concentration; and from 2.14 to 1.93 with decrease in gelling temperature. The samples were resilient with elastic stain at 1.2MPa of stress also decreased from 0.33 to 0.23 with increase in gelatin concentration. The crosslinker HMDI (hexamethylene diisocyanate) yielded more resilient samples at 1.2MPa in comparison to glutaraldehyde. Increased crosslinking time from 2 to 4h in continuous compression cycle show no improvement in maximum elastic stain of 1.2MPa stress. This surface elasticity of the scaffold enables the capacity of these materials for adherent self renewal and cultivation of the NTERA-2 cL.D1 (NT2/D1), pluripotent embryonal carcinoma cell with biomechanical surface, as is shown here. Proliferation with MG-63, ALP activity and Alizarin red mineralization assay on optimized scaffold demonstrated ***p<0.001 between different time points thus showing its potential for bone healing. In pre-clinical study histological bone response of the scaffold construct displayed improved activity of bone regeneration in comparison to self healing of control groups (sham) up to week 07 after implantation in rabbit tibia critical-size defect. Therefore, this nHA-CMChNa-GEL scaffold composite exhibits inherent and efficient physicochemical, mechanical and biological characteristics based on gel concentrations, gelatin mixing and gelling temperature thus points to creating bioactive 3D scaffolds with tunable elasticity for orthopedic applications.

Bifunctional Polysulfone-Chitosan Composite Hollow Fiber Membrane for Bioartificial Liver.

Hollow fiber membranes are widely used as assist devices for bioartificial liver application. Asymmetric porous polysulfone and polysulfone-tocopheryl polyethylene glycol succinate (Psf-TPGS) composite hollow fiber and flat membranes were prepared by phase inversion procedure and subsequently surface modified with chitosan using sulfonation with concentrated sulfuric acid. Sulfonation induces negative charge on the prepared membrane surface and facilitates the attachment of chitosan amine groups by electrostatic interaction. The surface modification of membrane is stable at room temperature as dictated by presence of nitrogen in XPS analysis and amide linkages in FT-IR spectra. Further, biological studies of the membranes were performed using HepG2 cell line. Chitosan is biocompatible and shows structural similarity to glycosaminoglycans, a native liver ECM component. The chitosan-modified composite Psf and Psf-TPGS membranes have shown enhanced attachment and proliferation of HepG2 cells on outer surface as confirmed by the cell counting, DNA content, confocal microscopy, and SEM micrographs. The cells form a 3D multicellular spheroid structure on the chitosan-modified membranes in significantly larger number as seen in the SEM micrographs. Also, the hemocompatibility of the modified composite membranes were comparable to the unmodified membranes. Thus, the chitosan-modified composite membranes we have developed are bifunctional and have the potential to be used in bioartifical liver application.