Perivascular Stem Cells: A Prospectively Purified Mesenchymal Stem Cell Population for Bone Tissue Engineering

Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formatio...

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Veröffentlicht in:Stem cells translational medicine 2012-06, Vol.1 (6), p.510-519
Hauptverfasser: James, Aaron W., Zara, Janette N., Zhang, Xinli, Askarinam, Asal, Goyal, Raghav, Chiang, Michael, Yuan, Wei, Chang, Le, Corselli, Mirko, Shen, Jia, Pang, Shen, Stoker, David, Wu, Ben, Ting, Kang, Péault, Bruno, Soo, Chia
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container_issue 6
container_start_page 510
container_title Stem cells translational medicine
container_volume 1
creator James, Aaron W.
Zara, Janette N.
Zhang, Xinli
Askarinam, Asal
Goyal, Raghav
Chiang, Michael
Yuan, Wei
Chang, Le
Corselli, Mirko
Shen, Jia
Pang, Shen
Stoker, David
Wu, Ben
Ting, Kang
Péault, Bruno
Soo, Chia
description Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone‐forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence‐activated cell sorting) of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient‐matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel‐like molecule 1 (NELL‐1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose‐derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell‐based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL‐1 is a candidate growth factor able to induce human PSC osteogenesis. Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering, but the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. Human perivascular stem cells (PSCs) were prospectively purified from adipose tissue, and their bone‐forming capacity was compared with that of traditionally derived SVF. It was found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. These studies suggest that adipose‐derived human PSCs are a new cell source for future efforts in skele
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However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone‐forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence‐activated cell sorting) of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient‐matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel‐like molecule 1 (NELL‐1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose‐derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell‐based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL‐1 is a candidate growth factor able to induce human PSC osteogenesis. Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering, but the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. Human perivascular stem cells (PSCs) were prospectively purified from adipose tissue, and their bone‐forming capacity was compared with that of traditionally derived SVF. It was found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. These studies suggest that adipose‐derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine.</description><identifier>ISSN: 2157-6564</identifier><identifier>EISSN: 2157-6580</identifier><identifier>DOI: 10.5966/sctm.2012-0002</identifier><identifier>PMID: 23197855</identifier><language>eng</language><publisher>United States: AlphaMed Press</publisher><subject>Adipogenesis ; Adipose tissue ; Adipose Tissue, White - cytology ; Adipose Tissue, White - metabolism ; Administrative support ; Adult stem cells ; Animals ; Antigens, CD34 - metabolism ; Bone growth ; Bone marrow ; Bone matrix ; Bone Matrix - metabolism ; Bone morphogenetic protein 2 ; Bone Morphogenetic Protein 2 - metabolism ; Bone Morphogenetic Protein 2 - pharmacology ; Bone Regeneration ; Calcium phosphates ; Calcium Phosphates - metabolism ; CD146 Antigen - metabolism ; CD34 antigen ; CD45 antigen ; Cell Culture Techniques ; Data analysis ; Defects ; Experiments ; FDA approval ; Flow Cytometry ; Humans ; Immunohistochemistry ; Inventors ; Laboratories ; Leukocyte Common Antigens - metabolism ; Lipectomy ; Male ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Mesenchymal Stromal Cells - metabolism ; Mesenchyme ; Mice ; Mice, SCID ; Morbidity ; Nerve Tissue Proteins - metabolism ; Osteoblast ; Osteogenesis ; Pericytes ; Pericytes - cytology ; Pericytes - drug effects ; Population ; Prospective Studies ; Recombinant Proteins - metabolism ; Recombinant Proteins - pharmacology ; Regenerative medicine ; Regenerative Medicine - methods ; Scholarships &amp; fellowships ; Stem cells ; Tissue engineering ; Tissue Engineering and Regenerative Medicine ; Tissue Scaffolds ; Tricalcium phosphate ; Writing ; X-Ray Microtomography</subject><ispartof>Stem cells translational medicine, 2012-06, Vol.1 (6), p.510-519</ispartof><rights>2012 AlphaMed Press</rights><rights>2012. 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However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone‐forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence‐activated cell sorting) of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient‐matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel‐like molecule 1 (NELL‐1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose‐derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell‐based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL‐1 is a candidate growth factor able to induce human PSC osteogenesis. Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering, but the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. Human perivascular stem cells (PSCs) were prospectively purified from adipose tissue, and their bone‐forming capacity was compared with that of traditionally derived SVF. It was found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. 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Zara, Janette N. ; Zhang, Xinli ; Askarinam, Asal ; Goyal, Raghav ; Chiang, Michael ; Yuan, Wei ; Chang, Le ; Corselli, Mirko ; Shen, Jia ; Pang, Shen ; Stoker, David ; Wu, Ben ; Ting, Kang ; Péault, Bruno ; Soo, Chia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4680-2326598dbf8878d0f3d5f96d40815d2df2e37007b385f342557b81736779559f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adipogenesis</topic><topic>Adipose tissue</topic><topic>Adipose Tissue, White - cytology</topic><topic>Adipose Tissue, White - metabolism</topic><topic>Administrative support</topic><topic>Adult stem cells</topic><topic>Animals</topic><topic>Antigens, CD34 - metabolism</topic><topic>Bone growth</topic><topic>Bone marrow</topic><topic>Bone matrix</topic><topic>Bone Matrix - metabolism</topic><topic>Bone morphogenetic protein 2</topic><topic>Bone Morphogenetic Protein 2 - metabolism</topic><topic>Bone Morphogenetic Protein 2 - pharmacology</topic><topic>Bone Regeneration</topic><topic>Calcium phosphates</topic><topic>Calcium Phosphates - metabolism</topic><topic>CD146 Antigen - metabolism</topic><topic>CD34 antigen</topic><topic>CD45 antigen</topic><topic>Cell Culture Techniques</topic><topic>Data analysis</topic><topic>Defects</topic><topic>Experiments</topic><topic>FDA approval</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Inventors</topic><topic>Laboratories</topic><topic>Leukocyte Common Antigens - metabolism</topic><topic>Lipectomy</topic><topic>Male</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Morbidity</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Osteoblast</topic><topic>Osteogenesis</topic><topic>Pericytes</topic><topic>Pericytes - cytology</topic><topic>Pericytes - drug effects</topic><topic>Population</topic><topic>Prospective Studies</topic><topic>Recombinant Proteins - metabolism</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Regenerative medicine</topic><topic>Regenerative Medicine - methods</topic><topic>Scholarships &amp; 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However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone‐forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence‐activated cell sorting) of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient‐matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel‐like molecule 1 (NELL‐1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose‐derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell‐based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL‐1 is a candidate growth factor able to induce human PSC osteogenesis. Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering, but the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. Human perivascular stem cells (PSCs) were prospectively purified from adipose tissue, and their bone‐forming capacity was compared with that of traditionally derived SVF. It was found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. These studies suggest that adipose‐derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine.</abstract><cop>United States</cop><pub>AlphaMed Press</pub><pmid>23197855</pmid><doi>10.5966/sctm.2012-0002</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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ispartof Stem cells translational medicine, 2012-06, Vol.1 (6), p.510-519
issn 2157-6564
2157-6580
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3659717
source Wiley Online Library Open Access
subjects Adipogenesis
Adipose tissue
Adipose Tissue, White - cytology
Adipose Tissue, White - metabolism
Administrative support
Adult stem cells
Animals
Antigens, CD34 - metabolism
Bone growth
Bone marrow
Bone matrix
Bone Matrix - metabolism
Bone morphogenetic protein 2
Bone Morphogenetic Protein 2 - metabolism
Bone Morphogenetic Protein 2 - pharmacology
Bone Regeneration
Calcium phosphates
Calcium Phosphates - metabolism
CD146 Antigen - metabolism
CD34 antigen
CD45 antigen
Cell Culture Techniques
Data analysis
Defects
Experiments
FDA approval
Flow Cytometry
Humans
Immunohistochemistry
Inventors
Laboratories
Leukocyte Common Antigens - metabolism
Lipectomy
Male
Mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - drug effects
Mesenchymal Stromal Cells - metabolism
Mesenchyme
Mice
Mice, SCID
Morbidity
Nerve Tissue Proteins - metabolism
Osteoblast
Osteogenesis
Pericytes
Pericytes - cytology
Pericytes - drug effects
Population
Prospective Studies
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacology
Regenerative medicine
Regenerative Medicine - methods
Scholarships & fellowships
Stem cells
Tissue engineering
Tissue Engineering and Regenerative Medicine
Tissue Scaffolds
Tricalcium phosphate
Writing
X-Ray Microtomography
title Perivascular Stem Cells: A Prospectively Purified Mesenchymal Stem Cell Population for Bone Tissue Engineering
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