Hylauronic Acid Scaffolds Promote Cardiac Function following Stem Cell Transplantation

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While the use of stem cells in organ regeneration has resulted in a number of treatments that have shown significant clinical promise, improving cardiac function using stem cells has not yet resulted in significant clinical leaps due to low levels of engrafment following injection of stem cells into damaged heart tissue.

With the purpose of improving stem cell retention in the myocardium following transplantation, a new study by Roselle Abraham’s lab at John Hopkins School of Medicine describes the development of a new hydrogel-based bio-adhesive and biodegradable scaffold to achieve such retention.

The manuscript, titled Hyaluronic Acid-Human Blood Hydrogels for Stem Cell Transplantation and published in Biomaterials, describes the synthesis of a hydrogel scaffold from lysed blood and HA, whose carboxyl groups are functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS). These carboxyl groups in turn react with primary amines from blood and tissue to form amide bonds, resulting in hydrogels that covalently bind to transplanted tissue while entrapping stem cells and retaining them in the transplanted site.

Beside physical characterization of hydrogels, the authors also performed in vivo studies with female rats induced with myocardial infarction. Animals treated with intra-myocardially-implanted HA-blood hydrogels could survive for a few hours after transplantation, and cell encapsulation in these hydrogels greatly increased acute myocardial retention for 1 hr post-transplantation.

Once transplanted, it is believed that growth factors present in the blood, as well as extracellular matrix proteins fibronectin and vitronectin, promote cell proliferation.

 

Representative 2-photon microscopy images illustrating live (green) and dead CDCs (red) on day 1 in HA-PEG (A) and HA-blood (human, lysed) hydrogels (B) and day 7 in HA-PEG (C) and HA-blood (D) hydrogels cultured in CEM E. Bar graphs summarize CDC survival at 1d and 1wk in HA-blood and HA-PEG hydrogels cultured in CEM F. HA-blood hydrogels, but not HA-PEG hydrogels permit CDC survival when cultured in Tyrode solution (containing glucose and electrolytes, but no serum) G. Picogreen assay revealed CDC proliferation on d4 and d8 in HA-blood hydrogels, but only on d8 in HA-PEG hydrogels

 

Unlike intra-myocardial injections, which typically result in cell loss from the injection site, epicardial cell delivery via scaffolds allows for the transplantation of large numbers of cells which are retained in the heart. While these studies were carried out with a single cell line on one organism, the authors believe that the scaffolds could provide a same robust substrate for various cell types including mesenchymal stem cells and endothelial progenitor cells. Furthermore, high mortality rates observed are still an issue that needs investigation.

To add to this body of work, contact us to discuss custom scaffold manufacturing, growth factors and extracellular matrix proteins that can support your 3D cell culture efforts.

 

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