Human Bone Marrow-Derived CD133⁺Cells Delivered to a Collagen Patch on Cryoinjured Rat Heart Promote Angiogenesis and Arteriogenesis

Abstract

Transplanting hematopoietic and peripheral blood-derived stem/progenitor cells can have beneficial effects in slowing the effects of heart failure. We investigated whether human bone marrow CD133+ -derived cells (BM-CD133 + cells) might be used for cell therapy of heart injury in combination with tissue engineering. We examined these cells for: 1) their in vitro capacity to be converted into cardiomyocytes (CMs), and 2) their potential for in vivo differentiation when delivered to a tissue-engineered type I collagen patch placed on injured hearts (group II). To ensure a microvascular network ready for use by the transplanted cells, cardiac injury and patching were scheduled 2 weeks before cell injection. The cardiovascular potential of the BM-CD133 + cells was compared with that of a direct injection (group I) of the same cells in heart tissue damaged according to the same schedule as for group II. While a small fraction (2 ± 0.5%) of BM-CD133 + cells cocultured with rat CMs switched in vitro to a CM-like cell phenotype, in vivo-and in both groups of nude rats transplanted with BM-CD133 + -there was no evidence of any CM differentiation (as detected by cardiac troponin I expression), but there were signs instead of new capillaries and small arterioles. While capillaries prevailed over arterioles in group II, the opposite occurred in group I. The transplanted cells further contributed to the formation of new microvessels induced by the patch (group II) but the number of vessels did not appear superior to the one developed after directly injecting the BM-CD133 + cells into the injured heart. Although chimeric human-rat microvessels were consistently found in the hearts of both groups I and II, they represented a minority (1.5-2.3%) compared with those of rat origin. Smooth muscle myosin isoform expression suggested that the arterioles achieved complete differentiation irrespective of the presence or absence of the collagen patch. These findings suggest that: 1) BM-CD133 + cells display a limited propensity for in vitro conversion to CMs; 2) the preliminarily vascularized bioscaffold did not confer a selective homing and differentiation advantage for the phenotypic conversion of BM-CD133 + cells into CMs; and 3) combined patching and cell transplantation is suitable for angiogenesis and arteriogenesis, but it does not produce better results, in terms of endothelial and smooth muscle cell differentiation, than the "traditional" method of cell injection into the myocardium.

Biomaterials for the Treatment of Myocardial Infarction

“…Callegari et al (7) showed that application of a collagen sponge to a rat cryoinjury model immediately post-injury led to increased angiogenesis, compared with the control, 15 and 60 days post-implantation of the patch. Additionally, delivery of human bone marrow-derived CD133 ϩ cells (4 ϫ 10 6 cells) with a collagen scaffold increased the number of vessels in a rat cryoinjury model; however, there was no significant differentiation into cardiomyocytes (8). Similarly, application of a collagen scaffold seeded with human mesenchymal stem cells (MSCs) (1 ϫ 10 6 cells) immediately post-infarction resulted in a 30% increase in fractional shortening (FS) in the patch-treated group compared with the control in a rodent model (9).…”

Hematopoietic Stem Cell Development, Niches, and Signaling Pathways

“…HSCs can also differentiate into other specialized cell or so called plasticity such as adipocytes [1], cardiomyocytes [2], endothelial cells [3], fibroblasts/myofibroblasts [4], liver cells [5, 6], osteochondrocytes [7, 8], and pancreatic cells [9]. Most HSCs are in quiescent state within the niches that maintain HSC pool and will respond to the signals after the balance of blood cells or HSC pool is disturbed from either intrinsic or extrinsic stimuli.…”

Biomaterial applications in cardiovascular tissue repair and regeneration

“…Delivering stem cells with biomaterials has become an increasingly popular method, and has developed into a field of its own. Numerous studies are testing biomaterials such as injectable hydrogels or patch material from natural and synthetic sources, or growth factors as solutions for maintaining stem cells to the wound site to improve engraftment and to aid in their survival and proliferation post-transplantation [40,56,93-95]. Most of these studies are at the preclinical stage.…”

“…In one study, human MSCs incorporated into a collagen patch-assisted engraftment decreased left ventricle systolic interior diameter, increased anterior wall thickness and increased fractional shortening by 30% [94]. In another study, human bone marrow CD133 + -derived cells transplanted on a collagen patch onto an injured heart resulted in formation of new microvessels, thought to be induced by the patch [95]. A mixture of growth factors was able to prolong survival of transplanted cardiomyocytes derived from human embryonic stem cells, improving cell engraftment after infarct [93].…”