Bone marrow Derived Pluripotent Cells are Pericytes which Contribute to Vascularization

Cai, Xiaoxiao; Lin, Yunfeng; Friedrich, Claudia C.; Neville, Craig M.; Pomerantseva, Irina; Sundback, Cathryn A.; Sharma, Parul; Zhang, Zhiyuan; Vacanti, Joseph P.; Hauschka, Peter V.; Grottkau, Brian E.

doi:10.1007/s12015-009-9097-6

Cited by 61 publications

(48 citation statements)

References 27 publications

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“…ASCs and BMSCs are similar in the expression of surface markers according to our study as well as previously published reports (7)(8)(9)29). Specifically, we found CD34, a surface marker of hematopoietic cells, negative or weakly positive, in both ASCs (8.23%) and BMSCs (10.13%), whereas CD146, a surface marker of mesenchymal stem cells, was positive in both (64.22% and 76.03%), implying a shared origin of ASCs and BMSCs.…”

Section: Discussionsupporting

confidence: 92%

“…Cai et al reported that BMSCs and ASCs were both smooth muscle actin (SMA) positive pericytes (7)(8), which agrees with Yang et al 's results that ASCs were CD34 negative and SMA positive, and belonged to a subset of pericytes (9). On the other hand, Lin et al claimed ASCs were CD34 posi-tive and SMA negative and thus, were not pericytes (10).…”

Section: Introductionmentioning

confidence: 56%

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Comparison of Effects of Mechanical Stretching on Osteogenic Potential of ASCs and BMSCs

et al. 2013

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Mechanical forces play critical roles in the development and remodeling processes of bone. As an alternative cell source for bone engineering, adipose-derived stem cells (ASCs) should be fully investigated for their responses to mechanical stress. Similarly, the osteogenic potential, stimulated by mechanical stress, should be compared with bone marrow stromal cells (BMSCs), which have been clinically used for bone tissue engineering. In this study, ASCs and BMSCs were osteogenic-induced for 48 hours, and then subjected to uniaxial mechanical stretching for 2 or 6 hours. Cell orientation, osteogenic regulatory genes, osteogenic genes and ALP activities were measured and compared between ASCs and BMSCs. ASCs could align in a perpendicular way to the direction of stretching stress, while BMSCs did not present a specific alignment. Both 2 and 6 hours mechanical stretching could enhance the mRNA expression of Osx and Runx2 in BMSCs and ASCs, while OCN mRNA only increased in ASCs after 6 hours mechanical loading. Mechanical stretching enhanced the BMP-2 mRNA expression in ASCs, while only after 6 hours of mechanical loading significantly increased the BMP-2 gene expression in BMSCs. Significant differences only exist between ASCs and BMSCs loaded at 2 hours of mechanical stretching. It is concluded that ASCs are more rapid responders to mechanical stress, and have greater potential than BMSCs in osteogenesis when stimulated by mechanical stretching, indicating their usefulness for bone study in a rat model. Keywords: mechanotransduction; stem cells; osteoblasts; adipocytes Bone Research (2013) 3: 282-290. doi: 10.4248/BR201303006 IntroductionBone mesenchymal stem cells (BMSCs) and adiposederived stem cells (ASCs) have both been used experimentally for gene therapy and tissue engineering applications ( 1-2). Currently, BMSCs are obtained by aspiration of 10-40 mL of bone marrow from the iliac crest, or at the time of bone marrow biopsy, and isolated by their adherence properties (3). ASCs can be obtained from subcutaneous adipose tissue by liposuction surgeries, and these procedures yield anywhere from 100 mL to 3L †These authors contributed equally to this work. Mechanical force is one of the fundamental biological factors that affect fracture healing and bone remodeling. Most studies report that mechanical stress promotes osteogenic differentiation of BMSCs or osteoblasts (14-21). Mechanical stress might also up-regulate the expression of osteogenic genes of ASC (22-25). Results from our previous study have shown that cyclic tensile mechanical loading of long duration could promote the expression of BMP-2 and Runx2 and thus, osteogenic differentiation of ASCs in osteogenic medium (26) or adipogenic medium (27). However, limited studies were found concerning a comparison of osteogenic potential, stimulated by mechanical stress between ASCs and BMSCs. Regarding the whole bone regeneration process being affected by mechanical stress, we determined that a comparison of osteogenic differentiation by mechanical stretching ...

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 56%

Comparison of Effects of Mechanical Stretching on Osteogenic Potential of ASCs and BMSCs

et al. 2013

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“…It is consistent with our previous finding using 2D imaging that hMSCs serve as pericytes. 31 However, in comparison, the 3D imaging provides better evidence for the role of hMSCs in stabilizing the microvessels formed by HUVECs.…”

Section: Discussionmentioning

confidence: 99%

Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by Video-Rate Intravital Microscopy and 3D Image Processing

Pang

Tsigkou

Spencer

et al. 2015

Tissue Engineering Part C: Methods

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Vascularization is a key challenge in tissue engineering. Three-dimensional structure and microcirculation are two fundamental parameters for evaluating vascularization. Microscopic techniques with cellular level resolution, fast continuous observation, and robust 3D postimage processing are essential for evaluation, but have not been applied previously because of technical difficulties. In this study, we report novel video-rate confocal microscopy and 3D postimage processing techniques to accomplish this goal. In an immune-deficient mouse model, vascularized bone tissue was successfully engineered using human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in a poly (d,l-lactide-co-glycolide) (PLGA) scaffold. Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in vivo to visualize the vascular structure in the engineered bone and the microcirculation of the blood cells. Postimage processing was applied to perform 3D image reconstruction, by analyzing microvascular networks and calculating blood cell viscosity. The 3D volume reconstructed images show that the hMSCs served as pericytes stabilizing the microvascular network formed by HUVECs. Using orthogonal imaging reconstruction and transparency adjustment, both the vessel structure and blood cells within the vessel lumen were visualized. Network length, network intersections, and intersection densities were successfully computed using our custom-developed software. Viscosity analysis of the blood cells provided functional evaluation of the microcirculation. These results show that by 8 weeks, the blood vessels in peripheral areas function quite similarly to the host vessels. However, the viscosity drops about fourfold where it is only 0.8 mm away from the host. In summary, we developed novel techniques combining intravital microscopy and 3D image processing to analyze the vascularization in engineered bone. These techniques have broad applicability for evaluating vascularization in other engineered tissues as well.

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“…It is well known that the main expression of ADAM12 may be observed during embryonic morphogenesis of skeletal muscles and visceral organs, and intriguingly this molecule may be newly expressed in several human fibrotic diseases 21,22,23,24,25,26 . Previously, we showed that because mesenchymal progenitors, which are generally considered an alternative source of functional pericytes 27,28 , exhibit the same phenotype and ability to differentiate of mature pericytes obtained from patients with SSc, they are involved in the generation of myofibroblasts in this disease 3,4,5,14 .…”

mentioning

confidence: 99%

Perivascular Cells in Diffuse Cutaneous Systemic Sclerosis Overexpress Activated ADAM12 and Are Involved in Myofibroblast Transdifferentiation and Development of Fibrosis

Cipriani

Benedetto²,

Ruscitti³

et al. 2016

J Rheumatol

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Objective.Microvascular damage is pivotal in the pathogenesis of systemic sclerosis (SSc), preceding fibrosis, and whose trigger is not still fully understood. Perivascular progenitor cells, with profibrotic activity and function, are identified by the expression of the isoform 12 of ADAM (ADAM12) and this molecule may be upregulated by transforming growth factor-β (TGF-β). The goal of this work was to evaluate whether pericytes in the skin of patients with diffuse cutaneous SSc (dcSSc) expressed ADAM12, suggesting their potential contribution to the fibrotic process, and whether TGF-β might modulate this molecule.Methods.After ethical approval, mesenchymal stem cells (MSC) and fibroblasts (FB) were isolated from bone marrow and skin samples collected from 20 patients with dcSSc. ADAM12 expression was investigated in the skin and in isolated MSC and FB treated with TGF-β by immunofluorescence, quantitative real-time PCR, and western blot. Further, we silenced ADAM12 expression in both dcSSc-MSC and -FB to confirm the TGF-β modulation.Results.Pericytes and FB of dcSSc skin showed an increased expression of ADAM12 when compared with healthy control skin. TGF-β in vitro treatment induced a significant increase of ADAM12 in both SSc-MSC and -FB, with the higher levels observed in dcSSc cells. After ADAM12 silencing, the TGF-β ability to upregulate α-smooth muscle actin in both SSc-MSC and SSc-FB was inhibited.Conclusion.Our results suggest that in SSc, pericytes that transdifferentiate toward activated FB are present in the vascular tree, and TGF-β, while increasing ADAM12 expression, may modulate this transdifferentiation.

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Bone marrow Derived Pluripotent Cells are Pericytes which Contribute to Vascularization

Cited by 61 publications

References 27 publications

Comparison of Effects of Mechanical Stretching on Osteogenic Potential of ASCs and BMSCs

Comparison of Effects of Mechanical Stretching on Osteogenic Potential of ASCs and BMSCs

Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by Video-Rate Intravital Microscopy and 3D Image Processing

Perivascular Cells in Diffuse Cutaneous Systemic Sclerosis Overexpress Activated ADAM12 and Are Involved in Myofibroblast Transdifferentiation and Development of Fibrosis

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