Abstract

The transcription factor p63 belongs to the p53 tumor suppressor family. However, p63 primarily regulates the proliferative potential of stem cells in epithelia. While studies have shown that p63 can exhibit both tumor suppressive and oncogenic properties in vitro, studies using knockout and transgenic mouse models have not linked p63 to tumor suppression or oncogenesis in vivo. Despite the rarity of p63 mutations in cancer, our previous study has shown a strong association between the splicing out of exon 4 of the p63 gene and epithelial tumor formation. Specifically, the loss of exon 4 leads to the activation of progenitor cells in epithelia, contributing to their malignant transformation. In experiments with mice lacking exon 4 of the p63 gene, we found that heterozygous mutants developed normally but displayed increased hyperplasia in certain epithelial tissues when exposed to carcinogens or oncogenic stimuli. Additionally, clonogenic culture of epithelia, developed for the skin grafts, has shown that progenitor cells in mutant epithelia exhibited hyper-proliferation compared to those in wild type counterpart. Overall, these findings underscore the critical role of p63 in tumor suppression in vivo and emphasizes the importance of splicing rather than gene mutation in compromising epithelial progenitor cell activity, ultimately leading to the development of precancerous conditions and, potentially, aggressive cancers such as squamous cell carcinomas.

Abstract

Title : Perivenular intracavernosal Mesenchymal stem cell ( MSC ) Isolation and storage from Corpora cavernosum and corpora spongiosum in adult male rabbit and adult dog and production of clonal MSC nanoparticulated delivery for penile condition which caused ED ( Erectile dysfunction ) in subject male rabbit and dog and check for the erection function in these male Dog and Rabbit

AIM : To prove the association of whether clonal MSC produced in GMP grade facility has role in ED treatment has value in regenerative medicine practice in Animals and thereby in humans.

Methodology : Taking 20 dogs and Rabbit as control and 20 as subjects ( Dogs/ rabbit) DMED ( Stretozocin induced diabetic ED) Male Dogs and Male Rabbits, they are subjected to clonal delivery of nanoparticulated MSC ( Mesenchymal Stem Cells ) . The ED function can be measured by intra cavernosal pressure measurement, apomorphine test, dynamic infusion caversometry, isometric tension study. The to be Stored MSC can be isolated and expanded in culture medium . After extraction these MSC cells are expanded to estimate the cytokine and biological response modifier functions and see for cytokine levels and regeneration mechanisms.

Discussion : The nanoparticulated Intracavernosal delivery of MSC can be used if proven superior and can be a potential treatment modality form DMED dogs and Rabbit Model.

Conclusion of the Hypothesis : The perivenular MSC taken from potent male Rabbits and Dogs might be able to change the ED status , once proven histologically the treatment could have a potential impact on the treatment of Human Male ED.

Abstract

Chronic musculoskeletal (MSK) pain is one of the most common medical complaints worldwide and musculoskeletal injuries have an enormous social and economical impact. Current pharmacological and surgical treatments aimed at relieving pain and restoring function are marginal. In addition, unsatisfactory outcomes and adverse effects are commonly reported. In order to find an accurate treatment to such pathologies, over the last years, there has been a significantly increasing interest in
cellular therapies, such as Platelet Rich Plasma, Bone Marrow Mesenchymal Stem Cells and adipose-derived mesenchymal stem cells (AMSCs). These cells represent a relatively new strategy in regenerative medicine, with many potential applications, especially regarding MSK disorders, and have become one of the leading disease modifying options for musculoskeletal diseases. There are preclinical and clinical
studies that demonstrate their safety efficacy in muscle, tendon, bone Spine and Joint regeneration.

This presentation aims to review the current state of autologous biologics therapies in the treatment of several MSK diseases and their clinical applications. Regenerative medicine interventions are applied to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous/allogeneic biologics and it continues to expand. The anti-inflammatory, immunomodulatory, and regenerative properties of bone marrow aspirate concentrates (Bone Marrow Mesenchymal Stem
Cells), Micro Fragmented Adipose tissue (Adipose MSC), and Platelet Rich Plasma have shown their therapeutic efficacy and safety in patients with severe chronic spine degeneration and joint disorders. Now, there are deeper investigations into the pathogenesis of the MSK diseases at the cellular level and the mechanisms of the biologics that could treat them.

There are several precision driven procedural techniques for delivery of the autologous biologics into the intervertebral disc of the spine or Subchondral bone of the joints or image guided intra-articular injection for better efficacy of biologics giving the patients’ better outcomes. Randomized control trials and metaanalysis studies have very good outcomes making biologics a viable option for nonsurgical treatments of spine and joint diseases.

Abstract

Chronic systemic organ failure is an important clinical problem with significant morbidity, mortality and socioeconomic impact worldwide. Unfortunately, there is no definitive or curative treatment for most of these conditions, and the management has been predominantly confined to supportive care, which necessitates the need for novel therapies. Mesenchymal stem cell (MSC) therapy has a vast array of preclinical data and early, preliminary clinical data that suggests its potential to regenerate and restore
the function of damaged tissues and organs.
To evaluate the effectiveness of MSC therapy in managing multiorgan failure, utilizing currently available literature. A review of human randomized controlled trials (RCTs) and observational studies assessing the role of MSC therapy in managing or treating organ failure.
PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1990 through May 2020. In this lecture, studies that included embryonic stem cells, induced pluripotent stem cells, differentiated MSCs into specific lineage cells, and hematopoietic stem cells were excluded. Trials with intraorgan infiltration of MSC were also excluded.
The primary outcome evaluated the improvement in clinical assessment scores and indices of organ function. The secondary outcome assessed the safety of MSC therapy in the clinical trials.