Preconditioning of human umbilical cord mesenchymal stem cells with deferoxamine potentiates the capacity of the secretome released from the cells and promotes immunomodulation and beta cell regeneration in a rat model of type 1 diabetes

Isildar B., Ozkan S., ŞAHİN H., ERÇİN M., Gezginci-Oktayoglu S., KOYUTÜRK M.

International Immunopharmacology, cilt.129, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 129
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.intimp.2024.111662
  • Dergi Adı: International Immunopharmacology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Conditioned medium, Immunomodulation, Mesenchymal stem cells, Preconditioning, Type 1 diabetes, β-cells
  • İstanbul Üniversitesi Adresli: Evet

Özet

This study aimed to examine the effects of the secretome released by human umbilical cord-mesenchymal stem cells (MSC) as a result of preconditioning with deferoxamine (DFX), a hypoxia mimetic agent, on type 1 diabetes (T1D), by comparing it with the secretome produced by untreated MSCs. Initially, the levels of total protein, IL4, IL10, IL17, and IFNγ in the conditioned medium (CM) obtained from MSCs subjected to preconditioning with 150 µM DFX (DFX-CM) were analyzed in comparison to CM derived from untreated MSCs (N-CM). Subsequently, the CMs were administered to rats with T1D within a specific treatment plan. Following the sacrification, immunomodulation was evaluated by measuring serum cytokine levels and assessing the regulatory T cell (Treg) ratio in spleen mononuclear cells. Additionally, β-cell mass was determined in the islets by immunohistochemical labeling of NK6 Homeobox 1 (Nkx6.1), Pancreatic duodenal homeobox-1 (Pdx1), and insulin antibodies in pancreatic sections. In vitro findings indicated that the secretome levels of MSCs were enhanced by preconditioning with DFX. In vivo, the use of DFX-CM significantly increased the Treg population, and accordingly, the level of inflammatory cytokines decreased. In β-cell marker labeling, D + DFX-CM showed significantly increased PDX1 and insulin immunoreactivity. In conclusion, while the factors released by MSCs without external stimulation had limited therapeutic effects, substantial improvements in immunomodulation and β-cell regeneration were seen with DFX-preconditioned cell-derived CM.