Stem Cells Therapy as a Possible Therapeutic Option in Treating COVID-19 Patients.

An unfortunate emergence of a new virus SARS-CoV-2, causing a disease known as COVID-19, has spread all around the globe and has caused a pandemic. It primarily affects the respiratory tract and lungs in some cases causing severe organ damage and pneumonia due to overwhelming immune responses. Clinical reports show that the most commons symptoms are fever, dry cough, and shortness of breath, along with several other symptoms. It is thought that an immense cytokine dysregulation in COVID-19 patients is caused following the virus infection. Notably, if patients present with pre-existing specific comorbidities like diabetes or high blood pressure, rates of COVID-19 induced complications and deaths are escalated. Mesenchymal stem cell (MSC) therapy has been shown to alleviate pneumonia and acute respiratory syndrome (ARDS) symptoms, through their immunomodulatory activities in COVID-19 patients. Although more research studies and clinical trial results are needed to elucidate the exact mechanism by which MSCs provide relief to COVID-19 infected patients. Results from clinical trials are encouraging as patients treated with MSCs, regain lung functions and have restored levels of cytokines and trophic factors underscoring the fact that stem cell therapy can be, at least, a complementary therapy to alleviate sufferings in COVID-19 patients. This review discusses the possible therapeutic uses of MSCs for treating COVID-19. Graphical Abstract.

Stem Cell Transplant for Advanced Stage Liver Disorders: Current Scenario and Future Prospects.

BACKGROUND: Chronic Liver Disorders (CLD), caused by the lifestyle patterns like alcoholism or by non-alcoholic fatty liver disease or because of virus-mediated hepatitis, affect a large population fraction across the world. CLD progresses into end-stage diseases with a high mortality rate. Liver transplant is the only approved treatment available for such end-stage disease patients. However, the number of liver transplants is limited due to the limited availability of suitable donors and the extremely high cost of performing the procedure. Under such circumstances, Stem Cell (SC) mediated liver regeneration has emerged as a potential therapeutic alternative approach. OBJECTIVE: This review aims to critically analyze the current status and future prospects of stem cellbased interventions for end-stage liver diseases. The clinical studies undertaken, the mechanism underlying therapeutic effects and future directions have been examined. METHOD: The clinical trial databases were searched at https://clinicaltrials.gov.in and http://www.isrctn.com to identify randomized, non-randomized and controlled studies undertaken with keywords such as "liver disorder and Mesenchymal Stem Cells (MSCs)", "liver cirrhosis and MSCs" and "liver disorder and SCs". Furthermore, https://www.ncbi.nlm.nih.gov/pubmed/ database was also explored with similar keywords for finding the available reports and their critical analyses. RESULTS: The search results yielded a significant number of studies that used bone marrow-derived stem cells, MSCs and hepatocytes. The studies clearly indicated that SCs play a key role in the hepatoprotection process by some mechanisms involving anti-inflammation, auto-immune-suppression, angiogenesis and anti-apoptosis. Further, studies indicated that SCs derived paracrine factors promote angiogenesis, reduce inflammation and inhibit hepatocyte apoptosis. CONCLUSION: The SC-based interventions provide a significant improvement in patients with CLD; however, there is a need for randomized, controlled studies with the analysis of a long-term follow-up.

Mesenchymal Stem Cell Conditioned Media Ameliorate Psoriasis Vulgaris: A Case Study.

Psoriasis, an autoimmune disease, affects a vast number of peoples around the world. In this report, we discuss our findings about a scalp psoriasis suffering patient with a Psoriasis Scalp Severity Index (PSSI) score of 28, who was treated with Mesenchymal stem cell conditioned media (MSC-CM). Remarkably, complete regression was recorded within a treatment period of one month only (PSSI score of 0). A number of bioactive factors like cytokines and growth factors secreted by MSCs in the conditioned medium are very likely to be the principle molecules which play a vital role in skin regeneration. Treatment using MSC-CM appears to be an effective tool for tackling the psoriatic problem and, thus, may offer a new avenue of therapy which could be considered as an alternative approach to overcome the limitations of the cell-based therapy.

An Overview on Stem Cells in Tissue Regeneration.

BACKGROUND: Deteriorations in tissues and decline in organ functions, due to chronic diseases or with advancing age or sometimes due to infections or injuries, can severely compromise the quality of life of an individual. Regenerative medicine, a field of medical research focuses on replacing non-functional or dead cells or repairing or regenerating tissues and organs to restore normal functions of an impaired organ. Approaches used in regenerative therapy for achieving the objective employ a number of means which include soluble biomolecules, stem cell transplants, tissue engineering, gene therapy and reprogramming of cells according to target tissue types. Stem cells transplant and tissue regeneration methods for treating various diseases have rapidly grown in usage over the past decades or so. There are different types of stem cells such as mesenchymal, hematopoietic, embryonic, mammary, intestinal, endothelial, neural, olfactory, neural crest, testicular and induced pluripotent stem cells. METHODS: This review covers the recent advances in tissue regeneration and highlights the application of stem cell transplants in treating many life-threatening diseases or in improving quality of life. RESULTS: Remarkable progress in stem cell research has established that the cell-based therapy could be an option for treating diseases which could not be cured by conventional medical means till recent. Stem cells play major roles in regenerative medicine with its exceptional characteristics of self-renewal capacity and potential to differentiate into almost all types of cells of a body. CONCLUSION: Vast number of reports on preclinical and clinical application of stem cells revealed its vital role in disease management and many pharmacological industries around the globe working to achieve effective stem cell based products.

Molecular characterization of secretory proteins Rv3619c and Rv3620c from Mycobacterium tuberculosis H37Rv.

Rv3619c and Rv3620c are the secretory, antigenic proteins of the ESAT-6/CFP-10 family of Mycobacterium tuberculosis H37Rv. In this article, we show that Rv3619c interacts with Rv3620c to form a 1 : 1 heterodimeric complex with a dissociation constant (K(d)) of 4.8 × 10(-7) M. The thermal unfolding of the heterodimer was completely reversible, with a T(m) of 48 °C. The comparative thermodynamics and thermal unfolding analysis of the Rv3619c-Rv3620c dimer, the ESAT-6-CFP-10 dimer and another ESAT family heterodimer, Rv0287-Rv0288, revealed that the binding strength and stability of Rv3619c-Rv3620c are relatively lower than those of the other two pairs. Molecular modeling and docking studies predict the structure of Rv3619c-Rv3620c to be similar to that of ESAT-6-CFP-10. Spectroscopic studies revealed that, in an acidic environment, Rv3619c and Rv3620c lose their secondary structure and interact weakly to form a complex with a lower helical content, indicating that Rv3619c-Rv3620c is destabilized at low pH. These results, combined with those of previous studies, suggest that unfolding of the proteins is required for dissociation of the complex and membrane binding. In the presence of membrane mimetics, the α-helical contents of Rv3619c and Rv3620 increased by 42% and 35%, respectively. In mice, the immune response against Rv3619c protein is characterized by increased levels of interferon-γ, interleukin-12 and IgG(2a) , indicating a dominant Th1 response, which is mandatory for protection against mycobacterial infection. This study therefore emphasizes the potential of Rv3619c as a subunit vaccine candidate.

RD antigen based nanovaccine imparts long term protection by inducing memory response against experimental murine tuberculosis.

BACKGROUND: The absence of certain genomic loci that are present in most of the virulent strains of Mycobacterium tuberculosis as well as lack of lasting memory responses are some of the major causes attributed to the non effectiveness of Bacille Calmette-Gue'rin (BCG) vaccine. Immunization schedules addressing these issues can offer better strategy for protection against tuberculosis. METHODS: The immunological responses evoked upon administration of archaeosome based antigen delivery system comprising T cell antigen, Rv3619c (an ESAT-6 family protein), has been assessed against experimental murine tuberculosis in BALB/c mice. RESULTS: Archaeosome based subunit vaccine has been found to elicit type-1 cytokines in the immunized mice. Besides effective T cell memory response, the Rv3619c based vaccine was able to reduce mycobacterial burden in the animals challenged with Mycobacterium tuberculosis infection. CONCLUSION: The data of the present study suggest that archaeosome encapsulated RD gene products offer substantial protection against M. tuberculosis infection.

Characterization of Rv3868, an essential hypothetical protein of the ESX-1 secretion system in Mycobacterium tuberculosis.

Rv3868, a conserved hypothetical protein of the ESAT-6 secretion system of Mycobacterium tuberculosis, is essential for the secretion of at least four virulence factors. Each protein chain is approximately 63 kDa and assembles into a hexamer. Limited proteolysis demonstrates that it consists of two domains joined by a linker. The N-terminal domain is a compact, helical domain of approximately 30 kDa and apparently functions to regulate the ATPase activity of the C-terminal domain and the oligomerization. The nucleotide binding site is situated in the C-terminal domain, which exhibits ATP-dependent self-association. It is also the oligomerization domain. Dynamic fluorescence quenching studies demonstrate that the domain is proximal to the C terminus in the apoprotein and exhibits a specific movement upon ATP binding. In silico modeling of the domains suggests that Arg-429 of a neighboring subunit forms a part of the binding site upon oligomerization. Mutational analysis of binding site residues demonstrates that the Arg-429 functions as the important "sensor arginine" in AAA-ATPases. Protein NMR experiments involving CFP-10 and activity assays rule out a general chaperone-like function for Rv3868. On the other hand, ATP-dependent "open-close" movements of the individual domains apparently enable it to interact and transfer energy to co-proteins in the ESX-1 pathway.

Solution structure and dynamics of peptidyl-tRNA hydrolase from Mycobacterium tuberculosis H37Rv.

Eubacterial peptidyl-tRNA hydrolase is an essential enzyme that hydrolyzes peptidyl-tRNAs that are released into the cytoplasm because of premature termination of translation, expression of minigenes, and action of lincosamide and macrolide antibiotics. This averts the arrest of protein synthesis caused by depletion of free tRNA. Recently, we demonstrated that Mycobacterium tuberculosis peptidyl-tRNA hydrolase (MtPth) is present in the cytosol of mycobacterium and is capable of hydrolyzing peptidyl-tRNA. Here, we present the solution structure of MtPth, which is the first solution structure for this family of proteins. MtPth typically consists of seven-stranded mixed beta-sheet surrounded by six alpha-helices. The backbone dynamics for this enzyme were probed by measuring (15)N relaxation parameters and these were analyzed with model-free formalism and reduced spectral density mapping analysis. Overall, the protein molecule has tau(m) of 9.67+/-0.02 ns. The (15)N relaxation data analysis reveals that while majority of the protein backbone is rigid to motions, a short segment consisting of enzymatically critical residue H22, the loop-helix cover over the active site crevice, and the C-terminal helical hairpin exhibit motions on the milli-to microsecond timescale, all of which are linked to interaction with the substrate peptidyl-tRNA.