The effects of transplanted cells in stem  cell therapy for myocardial ischemia

Pham, Truc Le-Buu; Pham, Phuc Van

doi:10.15419/bmrat.v3i11.136

Cited by 1 publication

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References 84 publications

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“…In addition to increased cell viability, this study showed that preconditioning by celastrol also increases MSC paracrine function. This key feature for effective cell therapy has involved proangiogenic, anti-inflammatory, and antiapoptotic cytokines [ 17 , 47 ]. In the case of ischemic diseases, proangiogenic paracrine activities contribute to wound healing by initiating cell proliferation, migration, and maturation for tissue revascularization [ 13 , 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Preconditioning Improves the Viability and Proangiogenic Paracrine Function of Hydrogel-Encapsulated Mesenchymal Stromal Cells

Touani

Borie

Azzi

et al. 2021

Stem Cells International

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The efficacy of cell therapy is limited by low retention and survival of transplanted cells in the target tissues. In this work, we hypothesize that pharmacological preconditioning with celastrol, a natural potent antioxidant, could improve the viability and functions of mesenchymal stromal cells (MSC) encapsulated within an injectable scaffold. Bone marrow MSCs from rat (rMSC) and human (hMSC) origin were preconditioned for 1 hour with celastrol 1 μM or vehicle (DMSO 0.1% v / v), then encapsulated within a chitosan-based thermosensitive hydrogel. Cell viability was compared by alamarBlue and live/dead assay. Paracrine function was studied first by quantifying the proangiogenic growth factors released, followed by assessing scratched HUVEC culture wound closure velocity and proliferation of HUVEC when cocultured with encapsulated hMSC. In vivo, the proangiogenic activity was studied by evaluating the neovessel density around the subcutaneously injected hydrogel after one week in rats. Preconditioning strongly enhanced the viability of rMSC and hMSC compared to vehicle-treated cells, with 90% and 75% survival versus 36% and 58% survival, respectively, after 7 days in complete media and 80% versus 64% survival for hMSC after 4 days in low serum media ( p < 0.05 ). Celastrol-treated cells increased quantities of proangiogenic cytokines compared to vehicle-pretreated cells, with a significant 3.0-fold and 1.8-fold increase of VEGFa and SDF-1α, respectively ( p < 0.05 ). The enhanced paracrine function of preconditioned MSC was demonstrated by accelerated growth and wound closure velocity of injured HUVEC monolayer ( p < 0.05 ) in vitro. Moreover, celastrol-treated cells, but not vehicle-treated cells, led to a significant increase of neovessel density in the peri-implant region after one week in vivo compared to the control (blank hydrogel). These results suggest that combining cell pretreatment with celastrol and encapsulation in hydrogel could potentiate MSC therapy for many diseases, benefiting particularly ischemic diseases.

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