Ameliorative effect of bone marrow-derived mesenchymal stem cells on burn-induced hepatic and metabolic derangements in rats

Life Sci. 2022 Oct 15:307:120891. doi: 10.1016/j.lfs.2022.120891. Epub 2022 Aug 23.

Abstract

Aims: The current study aims to investigate the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSCs) as a solo therapy in ameliorating both skin lesions and liver injury induced by cutaneous severe burn injury (SBI) in rats.

Main methods: In anesthetized male adult Wistar albino rats, 30 % total burn surface area and established hepatic injury was achieved via direct contact of each experimental animal's dorsum with heated metal rod (100 °C) for 10 s. On the next day following burn, human MSCs or mouse MSCs was administered locally around the burn site and intraperitonially (0.5 × 106 cells/rat for each route) and outcomes were investigated at 4 and 14 days following burn induction.

Key findings: Both types of MSCs significantly improved skin and liver histology, decreased liver enzymes, and ameliorated oxidative stress in hepatocytes of SBI-rats. Further, SBI-induced rises in hepatic apoptotic marker (caspase-3, Bax) and serum inflammatory markers (TNF-α, IL-1β, and IL-6) were reduced following either human or mouse MSC administration. In addition, MSCs augmented insulin receptor substrate-1, phosphorylated protein kinase-B (phospho-Akt), while alleviating serum glucose levels in SBI-rats. These previous effects persisted even at the 14-day time point.

Significance: Following single administration, bone marrow-derived MSCs is capable of counteracting SBI-induced skin lesions as well as related hepatic complications, specifically via mitigating postburn hyperglycemia and hyperinflammation.

Keywords: H(2)O(2) (PubChem CID: 784); Hematoxylin Eosin (PubChem CID: 86598188); Hyperglycemia; Hyperinflammation; Insulin receptor substrate-1; Ketamine HCl (PubChem CID: 381); Liver; Mesenchymal stem cells; Severe burn injury; Sodium pentobarbital (PubChem CID: 23676152).

MeSH terms

  • Animals
  • Bone Marrow / metabolism
  • Burns* / complications
  • Burns* / metabolism
  • Burns* / therapy
  • Caspase 3 / metabolism
  • Glucose / metabolism
  • Humans
  • Insulin Receptor Substrate Proteins / metabolism
  • Interleukin-6 / metabolism
  • Liver / metabolism
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells*
  • Mice
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Insulin Receptor Substrate Proteins
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Proto-Oncogene Proteins c-akt
  • Caspase 3
  • Glucose