Coronavirus disease 2019 (COVID-19) caused by novel Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2), is typically associated with severe respiratory distress and has claimed more than 525,000 lives already. The most fearful aspect is the unavailability of any concrete guidelines and treatment or protective strategies for reducing mortality or morbidity caused by this virus. Repurposing of drugs, antivirals, convalescent plasma and neutralizing antibodies are being considered for treatment but are still questionable in lieu of the conflicting data, study design and induction of secondary infections. Stem cell therapy has seen substantial advancements over the past decade for the treatment of various diseases including pulmonary disorders with severe complications similar to COVID-19. Recently, mesenchymal stem cells (MSCs) have received particular attention as a potential therapeutic modality for SARS-CoV2 infection due to their ability to inhibit cytokine storm, a hallmark of severe COVID-19. MSCs secretion of trophic factors and extracellular vesicles mediated intercellular signaling are considered as principal contributing factors for tissue recovery. Although, recent preliminary studies have established the safety and efficacy of these cells without any severe secondary complications in the treatment of SARS-CoV2 infection, the rational use of MSCs on a large scale would still require additional relevant clinical investigations and validation of postulated mechanisms of these cells. This review presents the current clinical findings and update on the potential use of stem cell therapy and its secretome in combating the symptoms associated with COVID-19.

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Advancing age is associated with several diseases and disorders due to multiorgan atrophy. The increasing proportion of elderly humans demands the identification of means to counteract aging and age‐associated disorders. There is an increased depletion of stem cells in the aged organs, resulting in their inability to repair the damage and hence organ degeneration. Stem cell therapy has been implicated in counteracting aging and shown promise. However, the use of stem cells encounters several side effects and complications such as handling and storage of the cells for transplantation purpose. Stem cells secretome has proven to be of significant importance in a variety of disorders. In this study, we have shown that secretome derived from dental pulp stem cells (DPSCs) can reverse the age‐associated degeneration induced by chronic exposure to d‐galactose in a rat model. The secretome was able to increase muscle grip strength and animal activity. Secretome also improved the kidney function and hepatic biochemistry similar to healthy controls as evaluated by renal function test and Fourier‐transform infrared spectroscopy. We also showed that secretome reduced the levels of monoamine oxidase and acetylcholinesterase in the brain and liver, indicating aging reversal. Finally, proteomic profiling of DPSCs secretome revealed the presence of 13 proteins which have antiaging functions. Thus, our study provides first proof of concept that DPSCs secretome can render protection against d‐galactose induced accelerated aging.

Osteoclastogenesis (OCG) is a multi-stage process that involves formation of activated osteoclasts from bone marrow macrophages. The progression of each stage of OCG is governed by a set of transcription factors and gene regulators, which are genetically and epigenetically regulated at both transcription and post-transcription levels. Epigenetic changes are used to denote interactions between genetic material and environment leading to phenotypic alterations that can be inherited, without any variations in DNA sequence. Epigenetic and transcription regulatory events have profound effects on osteoclast formation and activation; these have been implicated in numerous disorders including osteoporosis, osteopetrosis, rheumatoid arthritis, spondyloarthritis, gout and bone metastasis. We aim to conduct a systematic review to assess possible relationship between key epigenetic and transcriptional regulators of osteoclastogenesis, and their role in specific bone disorders. This is a protocol for the proposed review. Keywords: osteoclasts; osteoclastogenesis; epigenetics; transcription; bone; skeletal disorders; methylation; histone proteins; micro RNA

Musculoskeletal system accounts for the support, stability, and locomotion or movement of the human body. Musculoskeletal disorders (MSDs) include any injury, damage or disorder of muscles, bone, cartilage, tendons, ligaments, and joints in upper/ lower limbs or the back. Mesenchymal stem cells (MSCs) are being increasingly used for a variety of MSDs owing primarily to their excellent regenerative potential. The major mechanism through which MSCs participate in tissue repair is by the secretion of a broad repertoire of molecules which serve a myriad of biological functions. These molecules, collectively called as secretome, provide a way for cell free therapy by surpassing the limitations of cellular therapy and at the same time, provide equivalent benefits to the recipient. Cell free therapy utilizing only the secretome of MSCs has gained popularity in the past few years, and various preclinical studies have employed either the soluble factors, or vesicles, or complete secretome not only for disorders of musculoskeletal system but also of central nervous system, cardiac system, circulatory system, and autoimmunity. However, the exact mechanism of action of many of these molecules still remains to be discovered. Therefore, achieving an optimal outcome of tissue function restoration by designing a cell free therapeutic regimen using only secretome remains a major challenge. While acknowledging the potential of MSC secretome in other areas of regenerative medicine, this review will elucidate the regenerative potential of MSCs and their secretome in MSDs.