A perivascular origin for mesenchymal stem cells in multiple human organs

doi:10.1016/J.STEM.2008.07.003

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A perivascular origin for mesenchymal stem cells in multiple human organs

Journal Article•DOI•

A perivascular origin for mesenchymal stem cells in multiple human organs

Mihaela Crisan¹, Solomon Yap², Louis Casteilla², Louis Casteilla³, Chien Wen Chen², Mirko Corselli², Tea Soon Park², Gabriella Andriolo, Bin Sun², Bo Zheng², Li Zhang, Cyrille Norotte², Pang-ning Teng², Jeremy Traas⁴, Rebecca C. Schugar², Bridget M. Deasy², Stephen F. Badylak, Hans-Jörg Bühring⁵, Jean-Paul Giacobino², Lorenza Lazzari, Johnny Huard², Bruno Péault² - Show less +18 more•Institutions (5)

Boston Children's Hospital¹, University of Pittsburgh², Paul Sabatier University³, University of Pennsylvania⁴, University of Tübingen⁵

11 Sep 2008-Cell Stem Cell (Cell Press)-Vol. 3, Iss: 3, pp 301-313

TL;DR: Blood vessel walls harbor a reserve of progenitor cells that may be integral to the origin of the elusive MSCs and other related adult stem cells.

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About: This article is published in Cell Stem Cell.The article was published on 2008-09-11 and is currently open access. It has received 3638 citations till now. The article focuses on the topics: Stem cell transplantation for articular cartilage repair & Adult stem cell.

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Journal Article•DOI•

Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

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Simón Méndez-Ferrer¹, Tatyana V. Michurina², Francesca Ferraro³, Amin R. Mazloom¹, Ben D. MacArthur¹, Ben D. MacArthur⁴, Sergio A. Lira¹, David T. Scadden³, Avi Ma'ayan¹, Grigori Enikolopov², Paul S. Frenette⁵, Paul S. Frenette¹ - Show less +8 more•Institutions (5)

Icahn School of Medicine at Mount Sinai¹, Cold Spring Harbor Laboratory², Harvard University³, Centro Nacional de Investigaciones Cardiovasculares⁴, Albert Einstein College of Medicine⁵

12 Aug 2010-Nature

TL;DR: It is demonstrated that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.

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Abstract: The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin(+) MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent 'mesenspheres' that can self-renew and expand in serial transplantations. Nestin(+) MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or beta3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin(+) cells and favours their osteoblastic differentiation, in vivo nestin(+) cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin(+) MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin(+) cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.

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3,012 citations

Journal Article•DOI•

Pericytes: developmental, physiological, and pathological perspectives, problems, and promises.

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Annika Armulik¹, Guillem Genové¹, Christer Betsholtz¹•Institutions (1)

Karolinska Institutet¹

16 Aug 2011-Developmental Cell

TL;DR: The history of investigations into pericytes, the mural cells of blood microvessels, are reviewed, emerging concepts are indicated, and problems and promise are pointed out.

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2,120 citations

Cites background from "A perivascular origin for mesenchym..."

...However, whereas there is no doubt that MSCs can be isolated from perivascular locations in most—perhaps all—organs (Crisan et al., 2008b; Dellavalle et al., 2007; Tang et al., 2008), the question remains whether they are identical to the cells that a vascular biologist would refer to as pericytes....
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...A number of recent studies suggest that pericytes may constitute multipotent stem and/or progenitor cells, such as mesenchymal stem cells (MSCs) (Crisan et al., 2008b; Davidoff et al., 2004; Feng et al., 2011), white adipocyte progenitors (Olson and Soriano, 2011; Tang et al., 2008), muscle stem…...
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...Recent work has extended this concept to several other tissues in addition to bone marrow and dental pulp and provided further support for the notion that that MSCs derive from pericytes (Crisan et al., 2008a; Crisan et al., 2008b)....
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Journal Article•DOI•

Bone Tissue Engineering: Recent Advances and Challenges

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Ami R. Amini¹, Cato T. Laurencin¹, Syam P. Nukavarapu¹•Institutions (1)

University of Connecticut Health Center¹

01 Jan 2012-Critical Reviews in Biomedical Engineering

TL;DR: The fundamentals of bone tissue engineering are discussed, highlighting the current state of this field, and the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration.

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Abstract: The worldwide incidence of bone disorders and conditions has trended steeply upward and is expected to double by 2020, especially in populations where aging is coupled with increased obesity and poor physical activity. Engineered bone tissue has been viewed as a potential alternative to the conventional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice due to several limitations or challenges. Bone tissue engineering aims to induce new functional bone regeneration via the synergistic combination of biomaterials, cells, and factor therapy. In this review, we discuss the fundamentals of bone tissue engineering, highlighting the current state of this field. Further, we review the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration. Specifically, we discuss widely investigated biomaterial scaffolds, micro- and nano-structural properties of these scaffolds, and the incorporation of biomimetic properties and/or growth factors. In addition, we examine various cellular approaches, including the use of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), and their clinical application strengths and limitations. We conclude by overviewing the challenges that face the bone tissue engineering field, such as the lack of sufficient vascularization at the defect site, and the research aimed at functional bone tissue engineering. These challenges will drive future research in the field.

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1,742 citations

Journal Article•DOI•

Geometric cues for directing the differentiation of mesenchymal stem cells.

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Kristopher A. Kilian¹, Branimir Bugarija², Bruce T. Lahn², Milan Mrksich²•Institutions (2)

Howard Hughes Medical Institute¹, University of Chicago²

16 Mar 2010-Proceedings of the National Academy of Sciences of the United States of America

TL;DR: The role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates is pointed to.

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Abstract: Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature—and with each occupying the same area—display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.

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1,652 citations

Cites background from "A perivascular origin for mesenchym..."

...M stem cells (MSCs) are multipotent cells that were initially isolated from bone marrow and noted for their ability to differentiate into bone cells (osteoblasts), cartilage cells (chondrocytes), and fat cells (adipocytes) (1, 2)....
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Journal Article•DOI•

Satellite Cells and the Muscle Stem Cell Niche

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Hang Yin¹, Feodor D. Price¹, Michael A. Rudnicki¹•Institutions (1)

Ottawa Hospital Research Institute¹

01 Jan 2013-Physiological Reviews

TL;DR: For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved the understanding of skeletal muscle biology, with focuses on functions of satellite cells and their niche during the process ofletal muscle regeneration.

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Abstract: Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process invol...

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1,585 citations

Cites background from "A perivascular origin for mesenchym..."

...Intriguingly, cells carrying the same surface marks can be isolated from various tissues, including pancreas, adipose, and placenta and differentiate into skeletal muscle cells when cultured in vitro, irrespective of their origins (118)....
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...The fact that pericytes also display cell surface markers characteristic of mesenchymal stem cells (CD10 /CD13 / CD44 /CD73 /CD90 ) raised the hypothesis that pericytes may represent a significant portion of mesenchymal stem cells in the adult (85, 118, 163)....
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References

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Journal Article•DOI•

Multilineage Potential of Adult Human Mesenchymal Stem Cells

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Mark F. Pittenger, Alastair Morgan Mackay, Stephen C. Beck, Rama K. Jaiswal, Robin Douglas, Joseph D. Mosca, Mark Aaron Moorman, Donald William Jr. Ward Road Simonetti, Stewart Craig, Daniel R. Marshak¹ - Show less +6 more•Institutions (1)

Johns Hopkins University School of Medicine¹

02 Apr 1999-Science

TL;DR: Adult stem cells isolated from marrow aspirates of volunteer donors could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages.

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Abstract: Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

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20,479 citations

"A perivascular origin for mesenchym..." refers background in this paper

...Mesoangio- blasts and MDSCs may be related to other elusive, multilineage progenitor cells encountered in bone marrow and other tissues, such as MSCs (mesenchymal stem cells) (Caplan, 1991; Pittenger et al., 1999) and multipotent adult progenitor cells (MAPCs) (Jiang et al., 2002)....
[...]
...…placenta, umbilical cord, and cord blood and adipose tissue and can differentiate into me- soderm lineage cells, including myoblasts (Caplan, 1991; Pit- tenger et al., 1999); (2) muscle-derived MDSCs, which some of us have previously characterized (Qu-Petersen et al., 2002; Péault et al.,…...
[...]

Journal Article•DOI•

Human Adipose Tissue Is a Source of Multipotent Stem Cells

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Patricia A. Zuk¹, Min Zhu¹, Peter Ashjian¹, Daniel A. De Ugarte¹, Jerry I. Huang¹, Hiroshi Mizuno¹, Zeni Alfonso¹, John K. Fraser¹, Prosper Benhaim¹, Marc H. Hedrick¹ - Show less +6 more•Institutions (1)

University of California, Los Angeles¹

01 Dec 2002-Molecular Biology of the Cell

TL;DR: To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches and PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.

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Abstract: Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.

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6,473 citations

"A perivascular origin for mesenchym..." refers background in this paper

...…bone marrow-derived MAPCs, which can contribute to mesodermal, endodermal, and ectodermal cell lineages and have equivalents in mouse brain (Jiang et al., 2002), pancreas (Seaberg et al., 2004), and dermis (Toma et al., 2001) as well as in human skin (Shih et al., 2005) and WAT (Zuk et al., 2002)....
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Journal Article•DOI•

Mesenchymal stem cells

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Arnold I. Caplan¹•Institutions (1)

Case Western Reserve University¹

01 Sep 1991-Journal of Orthopaedic Research

TL;DR: The study of mesenchymal stem cells, whether isolated from embryos or adults, provides the basis for the emergence of a new therapeutic technology of self‐cell repair.

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4,861 citations

Journal Article•DOI•

Mesenchymal Stem Cells

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Gennady T. Sukhikh, V. V. Malaitsev, Bogdanova Im, I. V. Dubrovina

01 Feb 2002-Bulletin of Experimental Biology and Medicine

TL;DR: The bone marrow contains multipotent MSC, which can be easily isolated and cultured in vitro, and the possibility of their clinical use in cell and gene therapy is analyzed.

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Abstract: Institute of Biological Medicine, Moscow The formation of the concept of a mesenchymal stem cell (MSC) is a priority of Russian biological science. A. Ya. Fridenshtein and his colleagues were the first who experimentally proved the existence of MSC. Osteogenic potential of fibroblastlike bone marrow cells of different mammalian species was demonstrated [25,26]. Fibroblast-like bone marrow cells often formed discrete adhesive colonies in vitro [27,28,47]. After heteroand orthotopic transplantation in vivo cloned cells from these colonies formed bone, cartilaginous, fibrous, and adipose tissues [48]. Intensive self-renewal and multipotency of fibroblast-like colony-forming cells from the bone marrow allowed Fridenshtein and Owen to formulate a concept of multipotent mesenchymal precursor cells (MPC) [62]. An ordered chain of finely regulated cell proliferation, migration, differentiation, and maturation processes underlies the formation of the majority of cell lineages in adult organisms. The earliest cell elements in this chain are stem cells (SC). Along with extensive self-renewal capacity, SC possess a great differentiation potential. Apart from well studied hemopoietic and intestinal SC, other SC classes were recently discovered in adult organism. Until recently it was considered that SC in adults can give rise to cell lines specific to tissues where these cells are located; however, new facts necessitated revision of this concept. Hemopoietic SC capable of differentiating into all cell elements of the blood, can also be a source of hepatic oval cells [65]; neural SC, precursors of neurons and glia [2,3], serve as the source of early and committed hemopoietic precursors [10]. MSC, a source of bone, cartilaginous, and adipose tissue cells, can differentiate into neural cells [46]. Tissue growth and reparation are associated with migration of uncommitted precursor cells from other tissues. During muscle tissue reparation mesenchymal SC migrate from the bone marrow into skeletal muscles [24]. Hence, in addition to capacity to unlimited division and reproduction of a wide spectrum of descendants of a certain differentiation line, adult SC are characterized by high plasticity. The existence of a rare type of somatic pluripotent SC, common precursors of all SC in an adult organism, is hypothesized [79]. Another important characteristic of SC is their migration from the tissue niche into circulation, which was experimentally proven for hemopoietic and MSC [69,73]. For activation of the differentiation program, circulating SC should get into an appropriate microenvironment [75,78]. A potent stimulus for investigation of SC is the possibility of their clinical use in cell and gene therapy. The bone marrow contains multipotent MSC, which can be easily isolated and cultured in vitro. It is therefore interesting to analyze some fundamental aspects of MSC biology and the possibilities of their clinical use. MSC descendants are involved in the formation of bones, cartilages, tendons, adipose and muscle tissues, and stroma maintaining the hemopoiesis [12,19,51]. The term MPC is used to denote MSC and their committed descendants capable of differentiating into at least two types of mature cells, which are present in the bone marrow and some mesenchymal tissues [16,19,57,82].

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3,582 citations

"A perivascular origin for mesenchym..." refers background in this paper

...Mesoangio- blasts and MDSCs may be related to other elusive, multilineage progenitor cells encountered in bone marrow and other tissues, such as MSCs (mesenchymal stem cells) (Caplan, 1991; Pittenger et al., 1999) and multipotent adult progenitor cells (MAPCs) (Jiang et al., 2002)....
[...]
...…from bone marrow, placenta, umbilical cord, and cord blood and adipose tissue and can differentiate into me- soderm lineage cells, including myoblasts (Caplan, 1991; Pit- tenger et al., 1999); (2) muscle-derived MDSCs, which some of us have previously characterized (Qu-Petersen et al.,…...
[...]

Journal Article•DOI•

Self-Renewing Osteoprogenitors in Bone Marrow Sinusoids Can Organize a Hematopoietic Microenvironment

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Benedetto Sacchetti¹, Alessia Funari², Stefano Michienzi¹, Silvia Di Cesare, Stefania Piersanti, Isabella Saggio³, Isabella Saggio¹, Enrico Tagliafico, Stefano Ferrari, Pamela Gehron Robey⁴, Mara Riminucci², Paolo Bianco¹ - Show less +8 more•Institutions (4)

Sapienza University of Rome¹, University of L'Aquila², National Research Council³, National Institutes of Health⁴

19 Oct 2007-Cell

TL;DR: It is shown that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendOThelial cells within a miniature bone organ.

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2,093 citations

"A perivascular origin for mesenchym..." refers background or result in this paper

...Confirming and extending pre- vious observations (Ozerdem et al., 2002; Middleton et al., 2005; Sacchetti et al., 2007), we have validated the CD146+ NG2+ PDGFRb+ ALP+ CD34 CD45 vWF CD144 phenotype as an indicator of pericyte/perivascular cell identity throughout hu- man fetal and adult organs....
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...Interestingly, a population of CD146+ subendothelial cells in human bone mar- row contains osteogenic progenitors that are also at the origin of the stromal cells that support hematopoiesis (Sacchetti et al., 2007)....
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...…associated with pericytes during vascular morphogenesis (Ozerdem et al., 2002) and CD146 (aka S-endo1, Mel-CAM, Muc18, or gicerin), an endothelial cell antigen also expressed at the surface of peri- cytes (Li et al., 2003; Middleton et al., 2005; Sacchetti et al., 2007) (Figures 1A–1C and 1G)....
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...for Mesenchymal Stem Cells in Multiple Human Organs...
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