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Autologous MSCs: A Safe and Effective Treatment for Beta Cell Loss in Type 1 Diabetes?

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Review of “Type 1 Diabetes Mellitus Donor Mesenchymal Stromal Cells Exhibit Comparable Potency to Healthy Controls in Vitro” from Stem Cells Translational Medicine by Stuart P. Atkinson

Mesenchymal stem cell (MSC)-based therapeutics represent a potentially exciting means to inhibit the autoimmune destruction of pancreatic beta cells associated with Type 1 diabetes mellitus (T1D). This may occur via the immunomodulatory and anti-inflammatory capabilities of MSCs [1] or through the repair of remaining endogenous islets [2].

However, T1D has the potential to inhibit the function of patient-derived MSCs and so the team of Katarina Le Blanc (Karolinska University, Stockholm, Sweden) set out to compare the therapeutic potential of MSCs derived from T1D and healthy donors [3]. Their new Stem Cells Translational Medicine study highlights differences between T1D and healthy MSCs but demonstrates functional similarities which make T1D MSCs suitable for autologous therapy.

The study actually assessed two different types of BM-MSCs from different T1D donors; those with early stage disease (ET1D) and late-stage (LT1D) disease to make things really interesting. 

But what did Davies et al find in comparison to healthy donors?

  • Growth kinetics
    • No differences between control and T1D MSCs
  • Gene expression assessment via gene array
    • Altered expression of 30 transcripts in ET1D MSCs with no significant pathway enrichment
    • Altered expression of 211 transcripts in LT1D MSCs related to cytokine secretion, immunomodulatory activity, and wound healing.
  • Migratory responses to wounding
    • No differences between control and T1D MSCs
  • Immunomodulatory Phenotype
    • Multiple differences in cell responses to proinflammatory cytokine exposure
    • However, all MSCs retained a similar ability to suppress activation of T-cells in vitro
  • Hemocompatibility
    • LT1D MSCs exhibited overall improved hemocompatibility compared to control MSCs (See figure)

So despite gene expression differences and different responses to proinflammatory cytokines, T1D doesn’t appear to overtly affect the functionality (and therefore the therapeutic relevance) of BM-MSCs. Great news, as this report will enhance the impact of a clinical study by the same lab which demonstrated the safety of autologous MSC treatment in T1D patients [4] and, therefore, promotes MSC employment in autologous systemic therapy for pancreatic beta cell loss.

References

  1. Chhabra P and Brayman KL. Stem cell therapy to cure type 1 diabetes: from hype to hope. Stem Cells Transl Med 2013;2:328-336.
  2. Lee RH, Seo MJ, Reger RL, et al. Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci U S A 2006;103:17438-17443.
  3. Davies LC, Alm JJ, Heldring N, et al. Type 1 Diabetes Mellitus Donor Mesenchymal Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro. Stem Cells Translational Medicine 2016;5:1485-1495.
  4. Carlsson PO, Schwarcz E, Korsgren O, et al. Preserved beta-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes 2015;64:587-592.