Stem cell therapies and benefaction of somatic cell nuclear transfer cloning in COVID-19 era

Abstract

Background: The global health emergency of COVID-19 has necessitated the development of multiple therapeutic modalities including vaccinations, antivirals, anti-inflammatory, and cytoimmunotherapies, etc. COVID-19 patients suffer from damage to various organs and vascular structures, so they present multiple health crises. Mesenchymal stem cells (MSCs) are of interest to treat acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection.

Main body: Stem cell-based therapies have been verified for prospective benefits in copious preclinical and clinical studies. MSCs confer potential benefits to develop various cell types and organoids for studying virus-human interaction, drug testing, regenerative medicine, and immunomodulatory effects in COVID-19 patients. Apart from paving the ways to augment stem cell research and therapies, somatic cell nuclear transfer (SCNT) holds unique ability for a wide range of health applications such as patient-specific or isogenic cells for regenerative medicine and breeding transgenic animals for biomedical applications. Being a potent cell genome-reprogramming tool, the SCNT has increased prominence of recombinant therapeutics and cellular medicine in the current era of COVID-19. As SCNT is used to generate patient-specific stem cells, it avoids dependence on embryos to obtain stem cells.

Conclusions: The nuclear transfer cloning, being an ideal tool to generate cloned embryos, and the embryonic stem cells will boost drug testing and cellular medicine in COVID-19.

Keywords: Bio-pharming; COVID-19; Genome reprogramming; Regenerative medicine; SARS-CoV-2; SCNT; Stem cells.

Fig. 1

A simplified depiction of basic protocols of SCNT cloning showing monkey as NHP representative. SCNT pioneered a new era in stem cell engineering and cellular medicine by proving that it is possible to reprogram the genome of mature cells to a totipotent stage comparable to embryos. Here, COCs, cumulus oocytes complexes, i.e., immature oocytes; IVC, in vitro culture of cell-cytoplast couplets/embryos; IVM, in vitro maturation; HMC, handmade cloning; LOPU, laparoscopic ovum pick-up

Fig. 2

Various strategies: (a) SCNT reprogramming, (b) somatic cell fusion, and (c) induced pluripotency to reprogram patient-specific somatic cells to generate cells for regenerative medicine. Genetic methods viz., nucleic acids (NA), synthetic mRNA, non-nucleic methods (proteins and small molecules), and epigenetic modifiers such as vitamin C, 5-azacytidine, trichostatin A, valproic acid, sodium butyrate assist genome reprogramming. Compared to other methods, SCNT is a safe approach to generate NT-ESCs, which can be de-differentiated into other cell types

Fig. 3

Salient applications of reprogrammed cells in regenerative medicine, bio-pharming, and biomedical sciences. Human stem cell-derived organoids are important for testing host-virus interaction and screening efficacy of drug molecules against COVID-19. Here, 1, SCNT; 2, cell fusion; 3, induced pluripotency to generate iPSCs