Autologous transplantation of green tea epigallocatechin-3-gallate pretreated adipose-derived stem cells increases cardiac regenerative capability through C-X-C motif chemokine receptor 4 expression in the treatment of rats with diabetic cardiomyopathy

Tung‐Sheng Chen; Wei‐Wen Kuo; Chih‐Yang Huang

doi:10.1538/expanim.23-0109

January 1, 2024EXPERIMENTAL ANIMALSOpen Access

Autologous transplantation of green tea epigallocatechin-3-gallate pretreated adipose-derived stem cells increases cardiac regenerative capability through C-X-C motif chemokine receptor 4 expression in the treatment of rats with diabetic cardiomyopathy

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Why the study?

The detailed cellular mechanisms of stem cell transplantation coupled with epigallocatechin-3-gallate (EGCG) treatment in diabetic cardiomyopathy remain unclear.

Does autologous transplantation of EGCG-pretreated adipose-derived stem cells improve cardiac regenerative capability and function in a rat model of diabetic cardiomyopathy?

Structured PICO

Does autologous transplantation of EGCG-pretreated adipose-derived stem cells improve cardiac regenerative capability and function in a rat model of diabetic cardiomyopathy?

P

Population

Male Wistar rats (12 weeks old, 200-250g) with streptozotocin-induced diabetic cardiomyopathy, alongside in vitro models using adipose-derived stem cells (ADSC) and H9c2 cardiomyoblasts.

I

Intervention

Intravenous injection of 1 x 10^6 autologous adipose-derived stem cells (ADSC) pretreated with 10 μM green tea epigallocatechin-3-gallate (EGCG) for 3 hours.

C

Comparator

Sham (no diabetes), DM alone (untreated diabetic rats), and DM+ADSC (diabetic rats receiving 1 x 10^6 ADSC without EGCG pretreatment).

O

Outcome

Cardiac function (ejection fraction, fractional shortening), structural changes (fibrosis, disarray), and molecular markers (apoptosis, survival, hypertrophy) evaluated at 2 months post-transplantation.surrogate

Preconditioning adipose-derived stem cells with green tea EGCG enhances their cardiac regenerative capability via CXCR4 expression, significantly improving cardiac function and reducing fibrosis in a rat model of diabetic cardiomyopathy.

Implication

EGCG-pretreated ADSCs may enhance cardiac protection in diabetic rat models; leaves open translation to human diabetic cardiomyopathy.

Abstract

Cardiomyopathy is one of complications related to diabetes. Stem cell transplantation shows potential in diabetic cardiomyopathy treatment. Epigallocatechin-3-gallate (EGCG) is one of the major components found in green tea. Although stem cell transplantation and green tea EGCG supplementation show therapeutic effects on cardiomyopathy, the detailed cellular mechanisms in stem cell transplantation coupled with EGCG treatment remain unclear. This study investigates whether adipose-derived stem cells (ADSC) pretreated with EGCG show better protective effect on diabetic cardiomyopathy than ADSC without EGCG pretreatment. A cell model indicated that ADSC pretreated with EGCG increased cell functions including colony formation, migration and survival markers. All of these functions are blocked by small interfering C-X-C motif chemokine receptor 4 (siCXCR4) administration. These findings suggest that ADSC pretreatment with EGCG increases cell functions through CXCR4 expression. A diabetic animal model was designed to verify the above findings, including Sham, DM (diabetes mellitus), DM+ADSC (DM rats receiving autologous transplantation of ADSC) and DM+E-ADSC (DM rats receiving EGCG pretreated ADSC). Compared to the Sham, we found that all of pathophysiological signalings were activated in the DM group, including functional changes (decrease in ejection fraction and fractional shortening), structural changes (disarray and fibrosis) and molecular changes (increases in apoptotic, fibrotic, hypertrophic markers and decreases in survival and longevity markers). E-ADSC (DM+E-ADSC) transplantation shows significant improvement in the above pathophysiological signalings greater than ADSC (DM+ADSC). Therefore, ADSC pretreated with EGCG may contribute to clinical applications for diabetic patients with cardiomyopathy.