Stem Cell Research & Therapy (Jun 2024)

Single high-dose intravenous injection of Wharton’s jelly-derived mesenchymal stem cell exerts protective effects in a rat model of metabolic syndrome

  • Alvin Man Lung Chan,
  • Angela Min Hwei Ng,
  • Mohd Heikal Mohd Yunus,
  • Ruszymah Hj Idrus,
  • Jia Xian Law,
  • Muhammad Dain Yazid,
  • Kok-Yong Chin,
  • Mohd Rafizul Mohd Yusof,
  • See Nguan Ng,
  • Benson Koh,
  • Yogeswaran Lokanathan

DOI
https://doi.org/10.1186/s13287-024-03769-2
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 19

Abstract

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Abstract Background Metabolic syndrome (MetS) is a significant epidemiological problem worldwide. It is a pre-morbid, chronic and low-grade inflammatory disorder that precedes many chronic diseases. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) could be used to treat MetS because they express high regenerative capacity, strong immunomodulatory properties and allogeneic biocompatibility. This study aims to investigate WJ-MSCs as a therapy against MetS in a rat model. Methods Twenty-four animals were fed with high-fat high-fructose (HFHF) diet ad libitum. After 16 weeks, the animals were randomised into treatment groups (n = 8/group) and received a single intravenous administration of vehicle, that is, 3 × 106 cells/kg or 10 × 106 cells/kg of WJ-MSCs. A healthy animal group (n = 6) fed with a normal diet received the same vehicle as the control (CTRL). All animals were periodically assessed (every 4 weeks) for physical measurements, serum biochemistry, glucose tolerance test, cardiovascular function test and whole-body composition. Post-euthanasia, organs were weighed and processed for histopathology. Serum was collected for C-reactive protein and inflammatory cytokine assay. Results The results between HFHF-treated groups and healthy or HFHF-CTRL did not achieve statistical significance (α = 0.05). The effects of WJ-MSCs were masked by the manifestation of different disease subclusters and continuous supplementation of HFHF diet. Based on secondary analysis, WJ-MSCs had major implications in improving cardiopulmonary morbidities. The lungs, liver and heart show significantly better histopathology in the WJ-MSC-treated groups than in the untreated CTRL group. The cells produced a dose-dependent effect (high dose lasted until week 8) in preventing further metabolic decay in MetS animals. Conclusions The establishment of safety and therapeutic proof-of-concept encourages further studies by improving the current therapeutic model.

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