# Therapeutic Activities of Multipotent Stromal Cells for Islet Regeneration

**Authors:** Nazihah Rasiwala, Gillian I. Bell, Nouran N. Al-Banaa, David A. Hess

PMC · DOI: 10.3390/cells15060488 · 2026-03-10

## TL;DR

This paper explores how multipotent stromal cells may help regenerate insulin-producing cells in diabetes treatment.

## Contribution

The paper provides an in-depth analysis of the potential regenerative mechanisms of multipotent stromal cells in beta cell regeneration.

## Key findings

- MSC transplantation reduces hyperglycemia and aids islet repair in diabetes models.
- MSC secretome has immunomodulatory and pro-regenerative properties for pancreatic tissues.
- The mechanisms behind MSC-induced beta cell regeneration remain unclear and require further study.

## Abstract

Diabetes mellitus is a global healthcare issue of epidemic proportions. At the root of these disorders, characterized by poor glucose regulation and insulin deficiencies, is the pancreatic beta cell and insufficient insulin signal transduction in peripheral tissues. Residual c-peptide secretion and persisting beta cells have been found in patients who have been living with type 1 diabetes for over 50 years. Thus, beta cell regeneration has been vastly studied in rodents, and many agents to expand beta cell mass are under rigorous investigation for the treatment of diabetes. Multipotent stromal cells (MSC), isolated from human bone marrow, have an immunomodulatory and pro-regenerative secretome that can aid in repairing damaged tissues, including pancreatic islets. MSC transplantation has been shown to reduce hyperglycemia and orchestrate islet repair in experimental diabetes models and is currently being assessed in clinical trials. While the immunomodulatory mechanisms of MSC are well-studied, the beta-cell-regenerative mechanisms are unknown. MSC likely play a regenerative role by signaling to resident progenitor or precursor cells in the pancreas; however, the decades-long controversy surrounding the origin of regenerated adult beta cells remains unresolved. Herein, we take a deep dive into the role of MSC in the treatment of diabetes and the potential cellular mechanisms behind the MSC stimulation of beta cell regeneration.

## Linked entities

- **Diseases:** Diabetes mellitus (MONDO:0005015), type 1 diabetes (MONDO:0005147)

## Full-text entities

- **Genes:** Cd3e (CD3 antigen, epsilon polypeptide) [NCBI Gene 12501] {aka CD3, CD3epsilon, T3e}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Irs1 (insulin receptor substrate 1) [NCBI Gene 25467] {aka IRS1IRM}, Glp1r (glucagon-like peptide 1 receptor) [NCBI Gene 14652] {aka GLP-1R, GLP1Rc}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, cdm (cadmium resistance) [NCBI Gene 12582], Sox9 (SRY (sex determining region Y)-box 9) [NCBI Gene 20682] {aka 2010306G03Rik, mKIAA4243, mSox9}, THY1 (Thy-1 cell surface antigen) [NCBI Gene 7070] {aka CD90, CDw90}, HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, SFRP1 (secreted frizzled related protein 1) [NCBI Gene 6422] {aka FRP, FRP-1, FRP1, FrzA, SARP2}, BCL9 (BCL9 transcription coactivator) [NCBI Gene 607] {aka LGS}, Rip (regulation of phenobarbitol-inducible P450) [NCBI Gene 110628], Nes (nestin) [NCBI Gene 18008] {aka ESTM46, Ifaprc2, Marc2, RC2}, KRT19 (keratin 19) [NCBI Gene 3880] {aka CK19, K19, K1CS}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, UCN3 (urocortin 3) [NCBI Gene 114131] {aka SCP, SPC, UCNIII}, Mafa (MAF bZIP transcription factor A) [NCBI Gene 378435] {aka RIPE3b1}, Pdx1 (pancreatic and duodenal homeobox 1) [NCBI Gene 18609] {aka IDX-1, IPF-1, Ipf1, Mody4, STF-1, pdx-1}, Egf (epidermal growth factor) [NCBI Gene 13645], GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, Neurog3 (neurogenin 3) [NCBI Gene 11925] {aka Atoh5, Math4B, bHLHa7, ngn3}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Slc2a4 (solute carrier family 2 member 4) [NCBI Gene 25139] {aka Glut4}, Gast (gastrin) [NCBI Gene 14459] {aka GAS}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Car2 (carbonic anhydrase 2) [NCBI Gene 12349] {aka CAII, Ca2, Car-2, Ltw-5, Lvtw-5}, Gcg (glucagon) [NCBI Gene 14526] {aka GLP-1, Glu, PPG}, VTCN1 (V-set domain containing T cell activation inhibitor 1) [NCBI Gene 79679] {aka B7-H4, B7H4, B7S1, B7X, B7h.5, PRO1291}, Vim (vimentin) [NCBI Gene 22352], CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Insr (insulin receptor) [NCBI Gene 16337] {aka 4932439J01Rik, CD220, D630014A15Rik, IR, IR-A, IR-B}, Pax4 (paired box 4) [NCBI Gene 18506] {aka Pax-4}, Sst (somatostatin) [NCBI Gene 20604] {aka SOM, SRIF, SS, Smst}, Dclk1 (doublecortin-like kinase 1) [NCBI Gene 13175] {aka 1700113D08Rik, 2810480F11Rik, Click-I, Cpg16, Dcamkl1, Dcl}, Kit (Kit proto-oncogene receptor tyrosine kinase) [NCBI Gene 16590] {aka Bs, CD117, Fdc, Gsfsco1, Gsfsco5, Gsfsow3}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, Krt19 (keratin 19) [NCBI Gene 16669] {aka CK-19, EndoC, K19, Krt-1.19, Krt1-19}, WNT5A (Wnt family member 5A) [NCBI Gene 7474] {aka hWNT5A}, Arx (aristaless related homeobox) [NCBI Gene 11878] {aka Arx1}, Nkx6-1 (NK6 homeobox 1) [NCBI Gene 18096] {aka NKX6A, Nkx6.1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Procr (protein C receptor, endothelial) [NCBI Gene 19124] {aka Ccca, Ccd41, Epcr}, Hnf1b (HNF1 homeobox B) [NCBI Gene 21410] {aka HNF-1-beta, HNF-1B, HNF-1Beta, Hnf1beta, LFB3, Tcf-2}, SPON2 (spondin 2) [NCBI Gene 10417] {aka DIL-1, DIL1, M-SPONDIN, MINDIN}, WNT5B (Wnt family member 5B) [NCBI Gene 81029]
- **Diseases:** hypoglycemic (MESH:C000721848), severe combined immunodeficiency (MESH:D016511), ketoacidosis (MESH:D007662), SCID (MESH:D053632), overweight (MESH:D050177), diseases of the muscle, bone, and cartilage (MESH:D002357), metabolic disorders (MESH:D008659), autoimmune destruction (MESH:D008105), autoimmune (MESH:D001327), COVID-19 (MESH:D000086382), hyperplasia (MESH:D006965), AD (MESH:D018205), inflammation (MESH:D007249), neurological disorders (MESH:D009461), Hyperglycemia (MESH:D006943), loss of blood glucose homeostasis (MESH:D016063), metabolic and cardiovascular disturbances (MESH:D024821), kidney dysfunction (MESH:D007674), NOD (MESH:D009765), T2D (MESH:D003924), carotid, coronary, and peripheral artery disease (MESH:D002340), UC (MESH:C536938), injury to (MESH:D014947), pancreatic damage (MESH:D010182), insulin deficiencies (MESH:D007333), immunodeficient (MESH:D007153), Diabetes (MESH:D003920), non- (MESH:C580335), neuropathy (MESH:D009422), hyperosmolar coma (MESH:D006944), retinopathy (MESH:D058437), PANC (MESH:D010190), chronic pancreatitis (MESH:D050500), cardiovascular diseases (MESH:D002318), T1D (MESH:D003922), pancreatic injury (MESH:D010195), cognitive decline (MESH:D003072)
- **Chemicals:** blood glucose (MESH:D001786), CHIR99021 (MESH:C473711), glucose (MESH:D005947), sodium alginate (MESH:D000464), prostaglandin E2 (MESH:D015232), ATP (MESH:D000255), metformin (MESH:D008687), alloxan (MESH:D000496), STZ (MESH:D013311), iPAN (-), GABA (MESH:D005680), exendin-4 (MESH:D000077270)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Cercopithecidae (monkey, family) [taxon 9527], Rodentia (rodent, order) [taxon 9989], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** hTERT — Homo sapiens (Human), Transformed cell line (CVCL_E232), PANC — Homo sapiens (Human), Pancreatic adenosquamous carcinoma, Cancer cell line (CVCL_0384), C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025508/full.md

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Source: https://tomesphere.com/paper/PMC13025508