Growth factors-based beneficial effects of platelet lysate on umbilical cord-derived stem cells and their synergistic use in osteoarthritis treatment.

Abstract

Poor viability of mesenchymal stem cells (MSCs) at the transplanted site often hinders the efficacy of MSCs-based therapy. Platelet lysate (PL) contains rich amounts of growth factors, which benefits cell growth. This study aimed to explore how human PL benefits umbilical cord-derived MSCs (huc-MSCs), and whether they have synergistic potential in osteoarthritis (OA) treatment. As quality control, flow cytometry and specific staining were performed to identify huc-MSCs, and ELISA was used to quantify growth factors in PL. CCK-8 and flow cytometry assays were performed to evaluate the effects of PL on the cell viability and cell cycle progression of huc-MSCs. Wound healing and transwell assays were conducted to assess the migration of huc-MSCs. RNA sequencing, real time PCR, and Western blot assays were conducted to explore the growth factors-based mechanism of PL. The in vitro results showed that PL significantly promoted the proliferation, cell cycle, and migration of huc-MSCs by upregulating relevant genes/proteins and activating beclin1-dependent autophagy via the AMPK/mTOR signaling pathway. The main growth factors (PDGF-AA, IGF-1, TGF-β, EGF, and FGF) contributed to the effects of PL in varying degrees. The in vivo data showed that combined PL and huc-MSCs exerted significant synergistic effect against OA. The overall study determined the beneficial effects and mechanism of PL on huc-MSCs and indicated PL as an adjuvant for huc-MSCs in treating OA. This is the first report on the growth factors-based mechanism of PL on huc-MSCs and their synergistic application. It provides novel knowledge of PL's roles and offers a promising strategy for stem cell-based OA therapy by combining PL and huc-MSCs.

• Authors: Li Yan, Li Zhou, Bo Yan, Lei Zhang, Wenxi Du, Fucun Liu, Qiang Yuan, Peijian Tong, Letian Shan, Thomas Efferth
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 10 Pg. 857 (10 14 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 33057008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intercellular Signaling Peptides and Proteins

Topics

• Autophagy (drug effects)
• Blood Platelets (chemistry)
• Cord Blood Stem Cell Transplantation (methods)
• Humans
• Intercellular Signaling Peptides and Proteins (blood, isolation & purification, pharmacology)
• Mesenchymal Stem Cells (cytology, drug effects)
• Osteoarthritis (therapy)
• Stem Cells (cytology)
• Umbilical Cord (cytology)