2. Academic Validation
  3. Human platelet lysate enhances small lipid droplet accumulation of human MSCs through MAPK phosphorylation

Human platelet lysate enhances small lipid droplet accumulation of human MSCs through MAPK phosphorylation

  • Stem Cell Res Ther. 2024 Dec 18;15(1):473. doi: 10.1186/s13287-024-04085-5.
Ping Du # 1 2,  Xuelian Tao # 2,  Javad Harati 1 2 3,  Yue Shi 1 2,  Liang Xiao 4,  Xian Li 2,  Haobo Pan 5,  Peng-Yuan Wang 6 7
Affiliations

Affiliations

  • 1 Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.
  • 2 Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.
  • 3 Oujiang Laboratory, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
  • 4 Department of Surgery and Oncology, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China.
  • 5 Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China. hb.pan@siat.ac.cn.
  • 6 Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China. py.wang@ojlab.ac.cn.
  • 7 Oujiang Laboratory, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. py.wang@ojlab.ac.cn.
  • # Contributed equally.
PMID: 39696689 DOI: 10.1186/s13287-024-04085-5
Abstract

Background: Human platelet lysate (hPL) has emerged as a promising serum substitute to enhance the self-renewal and multipotency of human mesenchymal stem cells (MSCs). Despite its potential, the specific biological mechanisms by which hPL influences MSC phenotypes remain inadequately understood.

Methods: We investigated the biological signaling activated by hPL in two common types of human MSCs: bone marrow-derived MSCs (BMSCs) and adipose-derived MSCs (ASCs). Cell adhesion and cell-matrix interaction were assessed through immunofluorescence staining and western blotting. The impact of hPL on lipid droplet formation in MSCs was thoroughly examined using oil red O/BODIPY staining, semi-quantitative analysis, and qRT-PCR. RNA Sequencing and intracellular inhibition assays were also performed to elucidate the mechanisms by which hPL modulates MSC behavior.

Results: MSCs cultured in hPL medium demonstrated a reduction in cell size, spreading area, and vinculin puncta, while enhancing cell proliferation and lipid droplet accumulation compared to those cultured in control media. Notably, the lipid droplets in hPL-treated MSCs were significantly smaller than those in adipocyte-like cells differentiated from MSCs, highlighting hPL's distinctive role in lipid production. Gene and protein expression profiles of hPL-treated MSCs differed from those in adipocyte-like cells. An angiogenic factor array revealed that hPL-MSCs had a distinct angiogenic factor profile compared to FBS-MSCs, with VEGF expression closely linked to HIF-1α expression. RNA-seq data identified approximately 1,900 differentially expressed genes (DEGs) between hPL-MSCs and FBS-MSCs, with enrichment in focal adhesion, ECM-receptor interaction, and PI3K-Akt/MAPK signaling pathways. Inhibition of MAPK phosphorylation significantly hampered lipid formation in hPL-MSCs, underscoring the pivotal role of MAPK signaling in hPL-driven adipogenesis.

Conclusion: This study reveals the biological mechanisms by which hPL infleunces MSC behavior and differentiation, offering new insights into its potential application in regenerative medicine and tissue engineering.

Keywords

Focal adhesion; Human platelet lysate; Lipid droplet; MAPK phosphorylation; Mesenchymal stem cell (MSC).

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