TARGETED DELIVERY OF CYTOKINES, GROWTH FACTORS AND PRE-DIFFERENTIATED CELLS FOR MI TREATMENT
Loading...
Date
2023-12
Authors
Raziyeva, Kamila
Journal Title
Journal ISSN
Volume Title
Publisher
Nazarbayev University School of Medicine
Abstract
Following myocardial infarction (MI), cardiac tissue undergoes irreversible cellular
alterations, with cardiomyocytes being replaced by fibrotic tissue. To combat this our lab
synthesized a novel chitosan-based cryogel containing heparin and poly-vinyl alcohol, showcasing
distinct porosity and interconnected pore design. A novel cryogel system was previously
established as efficacious for tissue regeneration and sustained drug delivery and has been
optimized for the repair of cardiac tissue post-MI in a murine model.
The treatment regime involved the systematic loading and sequential injection of the
cryogel with specific cytokines, growth factors, and pre-differentiated cells. Initially, the cryogel
loaded with interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) was injected
intramyocardially immediately post-MI, targeting the acute inflammatory response. On day 4 post-
MI, a second injection was administered, this time utilizing cryogel loaded with vascular
endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2), aiming at promoting
tissue regeneration and neo-angiogenesis. Subsequently, on day 6 post-MI, the group received cells
previously differentiated from mouse mesenchymal stem cells: cardiomyocyte-like cells, smooth
muscle cells, and endothelial cells. These cells, in synergy with cytokines and growth factors, aim
to repopulate the lost cellular populations, thereby enhancing myocardial repair.
Our results highlighted significant myocardial repair in cohorts treated with the
combination of cryogel loaded with IL-10,TGF-β and VEGF,FGF-2 and pre-differentiated cells
(Cryo/GFs/Cells). Echocardiographic assessments revealed amplified ejection fraction, fractional
shortening, and reduced fibrotic regions, as confirmed by Masson Trichrome staining. Further
analyses confirmed the immunomodulatory and regenerative capacity of the treatment. Our novel
chitosan-based cryogel, enriched with anti-inflammatory and proangiogenic factors, serves as a
promising platform for the controlled release of therapeutics, significantly helping tissue repair and
regeneration post-MI. In addition, the separate administration of pre-differentiated cells acts in
synergy with the Cryo/GFs, further enhancing the regenerative process. The combination of
cellular therapy with the Cryo/GFs treatment provides a comprehensive approach for myocardial
recovery, using the unique benefits of both techniques to maximize the efficacy of the therapy.
Description
Keywords
Type of access: Open, MI, biomaterials, mesenchymal stem cells, tissue regeneration, cryogel
Citation
Raziyeva, K. (2023). Targeted delivery of cytokines, growth Factors and pre-differentiated cells for MI Treatment. Nazarbayev University School of Medicine