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Placenta-derived mesenchymal stem cells (P-MSCs) for COVID-19 pneumonia-a regenerative dogma.

ABSTRACT: With a robust rise in the number of COVID-19 cases, the World Health Organization (WHO) has declared COVID-19 as a pandemic on 11^th March 2020. COVID-19 pandemic has invited global researchers from various biomedical and biotechnological researchers to plan various treatment modalities for combating this pandemic crisis. At present, there is the unavailability of specific treatment modality; however, researchers have thrown light into the exploration of mesenchymal stem cells (MSCs) to therapeutically perquisite in ameliorating immune-mediated progressive worsening in COVID-19 infected patients. Cellular therapy (CT) has revolutionized the treatment of untreatable diseases with a better clinical and functional outcome. Placenta, being considered as medical waste, contains a variety of stem cells, and hence placenta-derived MSCs (P-MSCs) owe potentiality for extrapolation to combat COVID-19 pandemic. The usage of P-MSCs in combating the COVID-19 pandemic has plausible challenges in terms of isolation, harvesting, expansion, characterization, and involvement of ethical concerns. This article provides an insight into dealing COVID-19 pandemic with P-MSCs as cell-based therapy embracing immunomodulatory and immune-privileged potentials and future prospects. Advocating prospective randomized controlled clinical trials ethically will concretely supplement for its efficacy and safety concerns.

SUBMITTER: Siddesh SE

PROVIDER: S-EPMC7937692 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Placenta-derived mesenchymal stem cells (P-MSCs) for COVID-19 pneumonia-a regenerative dogma.

Siddesh Sushmitha Eachagattada SE Gowda Dheemant Muniswamy DM Jain Rashmi R Gulati Arun A Patil Goutham Shankargoud GS Anudeep Talagavadi Channaiah TC Jeyaraman Naveen N Muthu Sathish S Jeyaraman Madhan M

Stem cell investigation 20210203

With a robust rise in the number of COVID-19 cases, the World Health Organization (WHO) has declared COVID-19 as a pandemic on 11<sup>th</sup> March 2020. COVID-19 pandemic has invited global researchers from various biomedical and biotechnological researchers to plan various treatment modalities for combating this pandemic crisis. At present, there is the unavailability of specific treatment modality; however, researchers have thrown light into the exploration of mesenchymal stem cells (MSCs) t ...[more]

PMID: 33688491

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Project description:BackgroundThin endometrium is a primary cause of defective endometrial receptivity, resulting in infertility or recurrent miscarriage. Much effort has been devoted toward regenerating thin endometrium by stem cell-based therapies. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs with various advantages. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and possible underlying mechanisms.MethodsEthanol was injected into the mice uterus to establish the endometrium-injured model. The retention time of HP-MSCs and HA hydrogel was detected by in vivo imaging, while the distribution of HP-MSCs was detected by immunofluorescence staining. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry. In vitro studies were further conducted using EdU, transwell, tube formation, and western blot assays.ResultsInstilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri than normal HP-MSCs. In vivo studies showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness (P < 0.001, P < 0.05), decrease fibrous area (P < 0.0001), and promote the proliferation and angiogenesis of endometrial cells (as indicated by Ki67 and VEGF, P < 0.05, P < 0.05, respectively) in mice injured endometrium. HP-MSCs-HA could also significantly improve the embryo implantation rate (P < 0.01) compared with the ethanol group. Further mechanistic study showed the paracrine effects of HP-MSCs. They could not only promote the proliferation and migration of human endometrial stromal cells via the JNK/Erk1/2-Stat3-VEGF pathway but also facilitate the proliferation of glandular cells via Jak2-Stat5 and c-Fos-VEGF pathway. In turn, the increased VEGF in the endometrium promoted the angiogenesis of endothelial cells.ConclusionOur study suggested the potential therapeutic effects and the underlying mechanisms of HP-MSCs-HA on treating thin endometrium. HA hydrogel could be a preferable delivery method for HP-MSCs, and the strategy represents a promising therapeutic approach against endometrial injury in clinical settings.

Project description:BackgroundThe therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to humoral factors such as growth factors, cytokines, and chemokines. Human term placental tissue-derived MSCs (PlaMSCs), or conditioned medium left over from cultures of these cells, have been reported to enhance angiogenesis. Recently, the exosome, which can transport a diverse suite of macromolecules, has gained attention as a novel intercellular communication tool. However, the potential role of the exosome in PlaMSC therapeutic action is not well understood. The purpose of this study was to evaluate PlaMSC-derived exosome angiogenesis promotion in vitro and in vivo.MethodsMSCs were isolated from human term placental tissue by enzymatic digestion. Conditioned medium was collected after 48-h incubation in serum-free medium (PlaMSC-CM). Angiogenic factors present in PlaMSC-CM were screened by a growth factor array. Exosomes were prepared by ultracentrifugation of PlaMSC-CM, and confirmed by transmission electron microscopy, dynamic light scattering, and western blot analyses. The proangiogenic activity of PlaMSC-derived exosomes (PlaMSC-exo) was assessed using an endothelial tube formation assay, a cell migration assay, and reverse transcription-PCR analysis. The in-vivo angiogenic activity of PlaMSC-exo was evaluated using a murine auricle ischemic injury model.ResultsPlaMSC-CM contained both angiogenic and angiostatic factors, which enhanced endothelial tube formation. PlaMSC-exo were incorporated into endothelial cells; these exosomes stimulated both endothelial tube formation and migration, and enhanced angiogenesis-related gene expression. Laser Doppler blood flow analysis showed that PlaMSC-exo infusion also enhanced angiogenesis in an in-vivo murine auricle ischemic injury model.ConclusionsPlaMSC-exo enhanced angiogenesis in vitro and in vivo, suggesting that exosomes play a role in the proangiogenic activity of PlaMSCs. PlaMSC-exo may be a novel therapeutic approach for treating ischemic diseases.

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Placenta-derived mesenchymal stem cells (P-MSCs) for COVID-19 pneumonia-a regenerative dogma.

Publications

Placenta-derived mesenchymal stem cells (P-MSCs) for COVID-19 pneumonia-a regenerative dogma.

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