Injectable collagen scaffold promotes swine myocardial infarction recovery by long-term local retention of transplanted human umbilical cord mesenchymal stem cells

Abstract

Stem cell therapy is an attractive approach for recovery from myocardial infarction (MI) but faces the challenges of rapid diffusion and poor survival after transplantation. Here we developed an injectable collagen scaffold to promote the long-term retention of transplanted cells in chronic MI. Forty-five minipigs underwent left anterior descending artery (LAD) ligation and were equally divided into three groups 2 months later (collagen scaffold loading with human umbilical mesenchymal stem cell (hUMSC) group, hUMSC group, and placebo group (only phosphate-buffered saline (PBS) injection)). Immunofluorescence staining indicated that the retention of transplanted cells was promoted by the collagen scaffold. Echocardiography and cardiac magnetic resonance imaging (CMR) showed much higher left ventricular ejection fraction (LVEF) and lower infarct size percentage in the collagen/hUMSC group than in the hUMSC and placebo groups at 12 months after treatment. There were also higher densities of vWf-, α-sma-, and cTnT-positive cells in the infarct border zone in the collagen/cell group, as revealed by immunohistochemical analysis, suggesting better angiogenesis and more cardiomyocyte survival after MI. Thus, the injectable collagen scaffold was safe and effective on a large animal myocardial model, which is beneficial for constructing a favorable microenvironment for applying stem cells in clinical MI. injectable collagen scaffold, mesenchymal stem cell, MI

Targeted Myocardial Restoration with Injectable Hydrogels—In Search of The Holy Grail in Regenerating Damaged Heart Tissue

“…This would suggest that injectable hydrogels have the ability to retain the highly complex and intricate architecture of the heart post-MI, resulting in increased EF [ 2 ]. This would be in line with the findings of studies [ 13 , 14 , 15 , 16 , 17 , 18 , 20 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 30 ], which reported both attenuated LV remodeling and an increase in EF.…”

“…The common modalities used to measure these parameters included: echocardiography, MRI, and immunohistochemistry. Out of the 21 studies, Giordano et al, 2013 [ 19 ], Yamamoto et al, 2001 [ 20 ], Zhou et al, 2012 [ 10 ], Liu et al, 2006 [ 11 ], and Takehara et al, 2008 [ 29 ] did not measure the direct effect of treatment on LV remodeling. The remaining 16 studies that looked into LV remodeling reported either attenuated or equivocal LV remodeling.…”

“…Cell types, including skeletal myoblasts (SKMs), CMs, and other progenitor cells capable of differentiation to CMs, like embryonic stem cells (ESCs), ESC-derived CMs (ESCCMs), and mesenchymal stem cells (MSCs) with limited potentials, were investigated. Human umbilical mesenchymal stem cells [hUMSC] are a new focus [ 20 ], whereas basic fibroblast growth factor (bFGF), acidic gelatin hydrogel microspheres (AGHM), and vascular endothelial growth factor (VEGF) are in use with non-superiority to each other. Vu et al used hyaluronic acid-based hydrogel coupled with PRP and showed improved host-cell viability [ 30 ]; while Traverse et al [ 18 ] reported the first-in-human study with VentriGel TM (ECM from the decellularized porcine myocardium) in patients with 1st STEMI treated by PCI within a period of post-intervention between 60 days and 3 years, and found MRI evidence of LV remodeling and a clinical improvement in the study subgroup.…”

Injectable Hydrogels for Improving Cardiac Cell Therapy—In Vivo Evidence and Translational Challenges

“…Most studies comparing the in vivo effect of cells administered in saline with cells administered in hydrogels report an improved beneficial effect in the hydrogel group (Table 2). Furthermore, the majority of recent studies report cell therapy to have a positive effect on LVEF and a larger effect size when administering cells in hydrogel compared to the non-treated group [10,12,15,17,[51][52][53][54][55][56][57]. Other studies found no benefit of cell therapy alone, but only a functional effect of cells in hydrogels [10,[13][14][15][16]48,[58][59][60][61][62].…”

“…Other studies found no benefit of cell therapy alone, but only a functional effect of cells in hydrogels [10,[13][14][15][16]48,[58][59][60][61][62]. A direct comparison between the cell-only group and the cell in hydrogel found significant functional benefits of administration in the hydrogel [10,[12][13][14][15][16][17]48,[51][52][53][54]56,57,[61][62][63]. A few of the recent studies included both a cell-only control and a hydrogel-only control.…”