Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue

Müller, A; Mehrkens, Arne; Schäfer, Dirk; Jaquiéry, Claude; Güven, Sinan; Lehmicke, Michael; Martinetti, Roberta; Farhadi, I; Jakob, Marcel; Scherberich, Arnaud; Martín, Iván

doi:10.22203/ecm.v019a13

Cited by 103 publications

(107 citation statements)

References 28 publications

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“…However, VFB grafts are generated from the patient's own fibula, resulting in additional morbidity associated with the procedure. As a result, current tissue engineering efforts focus on developing synthetic bone grafts with preformed, functional vascular networks (124)(125). Before implantation, mineral deposition in these grafts is spatially associated with the vascular network, consistent with the hypothesis that vascularized bone grafts improve subsequent bone formation (126).…”

Section: Blood Flow In Bone Graftsmentioning

confidence: 84%

Skeletal Blood Flow in Bone Repair and Maintenance

2013

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Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anatomy, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups. IntroductionThe rate at which blood vessels deliver oxygen, nutrients, growth factors, and circulating cells to boneis tightly regulated as a function of blood pressure and vascularizaAll biological tissues, including bone, require vascular support to survive. However, a frequently overlooked feature of bone is its extensive vascular network. Many studies have demonstrated that the blood vessels in bone are necessary for nearly all skeletal functions, including development, homeostasis, and repair (1). In addition, blood vessels lost due to trauma are regenerated, and new bone tissue formed in response to injury is vascularized. As a consequence of this environment, the blood vessels in bone are highly active, not simply a passive source for the delivery of nutrients (2). Readers are referred to recent publications for more information about the active processes of the vasculature not covered in this review, including the vascular niche and hypoxia-driven signaling pathways (3-4). tion. Given that blood pressure is generally maintained, the number and size of blood vessels determines the local blood flow rate. These two factors are regulated through the processes of angiogenesis and vasomotor function, respectively. Although a variety of skeletal disorders are associated with general vascular dysfunction (5-7), this review will focus on the regulation of bone blood flow, through the number and size of vessels, during bone repair and regeneration. To introduce this topic, the skeletal vascular anatomy and techniques for measuring bone blood flow are briefly discussed. Blood supply in boneA dense vascular network delivers oxygen and nutrients to all 206 bones in the human body. In general, this requires a substantial portion of the total cardiac output. Experimental work in various animal species has demonstrated that a significant portion of the resting cardiac output is directed to the skeleton, likely between 10% and 15% (8-12).For some time, the blood flow pattern in bones has been described as primarily centrifugal: blood is supplied to the cortical bone through the nutrient arteries in the (Figure 1), and returned by the periosteal veins (13). Particularly in long bones, the vascular anatomy is well characterized, wi...

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Section: Blood Flow In Bone Graftsmentioning

confidence: 84%

Skeletal Blood Flow in Bone Repair and Maintenance

2013

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“…Likewise, Follmar et al 113 saw limited angiogenesis and no evidence of ossification in ADSCsloaded fibrin glues implanted subcutaneously in rabbits. Muller et al 114 observed some evidence of combined angiogenesis and osteoid structures, identified with histology and immunostaining for bone sialoprotein and osteocalcin, in human ADSC-loaded fibrin glues combined with betatricalcium phosphate, hydroxyapatite, and acellular bone xenografts implanted subcutaneously in nude mice. However, the authors found no evidence of murine derived bone structures in the implants, indicating a lack of osteoinductivity.…”

Section: Incorporating Scbts Into the Designmentioning

confidence: 99%

“…However, the authors found no evidence of murine derived bone structures in the implants, indicating a lack of osteoinductivity. 114 More recent data from the same group indicated that SVF combined with 250 ng of BMP-2 and encapsulated in a fibrin and porous calcium phosphate composite gel could form heterotropic bone when injected subcutaneously in nude mice. 115 Overall, this combined evidence suggests that additional inductive stimulation of stem cells within the brief surgical time frame may be crucial in improving efficacy of intraoperative designs.…”

Section: Incorporating Scbts Into the Designmentioning

confidence: 99%

Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

Dennis

Berkland

Bonewald

et al. 2015

Tissue Engineering Part B: Reviews

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“…A particularly interesting target tissue for reconstructive surgery in the context of vascularization seem to be grafts vascularized in a onestep procedure. The first promising studies aiming to develop an osteogenic and vasculogenic construct using human adipose stromal-vascular cell fractions were performed by Martin et al from Basel University Hospital [66,69]. They demonstrated that human ASCs under perfusion flow in a three-dimensional environment are able to form bone tissue and blood vessels after implantation in nude mice.…”

Section: Endothelial Differentiationmentioning

confidence: 99%

“…Human ASCs in vitro [19] Human ASCs in athymic nude rats [39] Chondrogenic differentiation Human ASCs in vitro [56,57,91,92] Human ASCs in SCID mice [54] Osteogenic differentiation Human ASCs in vitro [93][94][95][96] Human ASCs in nude mice [97] Human ASCs in SCID mice [19,98] Human ASCs in athymic mice [45] Human ASCs in rats [75] Rat ASCs in SD rats [40] Myogenic differantiation Human ASCs in vitro [60,[99][100][101] Human ASCs in mdx mice [102] Human ASCs in nude mice [34] Cardiomyogenic differentiation Human ASCs in vitro [103,104] Rat ASCs in rats [105] Neuronal differentiation Human ASCs in vitro [43,106] Canine ASCs in dogs with spinal cord injuries [107] Rat ASCs in rats [70] Osteogenic constructs with intrinsic vascularization Human ASCs in nude mice [66,69] Epithelial differentiation Human ASCS in vitro [59,74] Kidney differentiation Human ASCs in C57BL/6 mice [108] Pancreatic differentiation Human ASCs in vitro [72,73] Hepatocyte differentiation Human ASCs in Pfp/Rag2 knockout mice [77] Human ASCs in Ccl4 mice [76] Periodontal tissue regeneration Rat ASCs in rats [109] The proposed uses for ASCs in tissue engineering and regenerative medicine are collected in Tab. 1.…”

Section: Neuronal Differentiationmentioning

confidence: 99%

Stem cells from adipose tissue

Witkowska-Zimny

Walenko

2011

Cellular and Molecular Biology Letters

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This is a review of the growing scientific interest in the developmental plasticity and therapeutic potential of stromal cells isolated from adipose tissue. Adipose-derived stem/stromal cells (ASCs) are multipotent somatic stem cells that are abundant in fat tissue. It has been shown that ASCs can differentiate into several lineages, including adipose cells, chondrocytes, osteoblasts, neuronal cells, endothelial cells, and cardiomyocytes. At the same time, adipose tissue can be harvested by a minimally invasive procedure, which makes it a promising source of adult stem cells. Therefore, it is believed that ASCs may become an alternative to the currently available adult stem cells (e.g. bone marrow stromal cells) for potential use in regenerative medicine. In this review, we present the basic information about the field of adipose-derived stem cells and their potential use in various applications.

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Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue

Cited by 103 publications

References 28 publications

Skeletal Blood Flow in Bone Repair and Maintenance

Skeletal Blood Flow in Bone Repair and Maintenance

Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

Stem cells from adipose tissue

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