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Journal ArticleDOI

Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells

TL;DR: Adipose-derived cells have the potential to differentiate into functional smooth muscle cells and, thus, adipose tissue can be a useful source of cells for treatment of injured tissues where smooth muscle plays an important role.
Abstract: Smooth muscle is a major component of human tissues and is essential for the normal function of a multitude of organs including the intestine, urinary tract and the vascular system. The use of stem cells for cell-based tissue engineering and regeneration strategies represents a promising alternative for smooth muscle repair. For such strategies to succeed, a reliable source of smooth muscle precursor cells must be identified. Adipose tissue provides an abundant source of multipotent cells. In this study, the capacity of processed lipoaspirate (PLA) and adipose-derived stem cells to differentiate into phenotypic and functional smooth muscle cells was evaluated. To induce differentiation, PLA cells were cultured in smooth muscle differentiation medium. Smooth muscle differentiation of PLA cells induced genetic expression of all smooth muscle markers and further confirmed by increased protein expression of smooth muscle cell-specific α actin (ASMA), calponin, caldesmon, SM22, myosin heavy chain (MHC), and smoothelin. Clonal studies of adipose derived multipotent cells demonstrated differentiation of these cells into smooth muscle cells in addition to trilineage differentiation capacity. Importantly, smooth muscle-differentiated cells, but not their precursors, exhibit the functional ability to contract and relax in direct response to pharmacologic agents. In conclusion, adipose-derived cells have the potential to differentiate into functional smooth muscle cells and, thus, adipose tissue can be a useful source of cells for treatment of injured tissues where smooth muscle plays an important role.
Citations
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Journal ArticleDOI
TL;DR: A closer look at the diversity of smooth muscle origins in vascular development provides new perspectives about how blood vessels differ from one another and why they respond in disparate ways to common risk factors associated with vascular disease.
Abstract: The origins of vascular smooth muscle are far more diverse than previously thought. Lineage mapping studies show that the segmental organization of early vertebrate embryos leaves footprints on the adult vascular system in the form of a mosaic pattern of different smooth muscle types. Moreover, evolutionarily conserved tissue forming pathways produce vascular smooth muscle from a variety of unanticipated sources. A closer look at the diversity of smooth muscle origins in vascular development provides new perspectives about how blood vessels differ from one another and why they respond in disparate ways to common risk factors associated with vascular disease.

657 citations

Journal ArticleDOI
TL;DR: This study shows that human endometrium contains a small population of MSC-like cells that may be responsible for its cyclical growth, and may provide a readily available source of M SC for tissue engineering applications.
Abstract: BACKGROUND: Human endometrium has immense regenerative capacity, growing ~5 mm in 7 days every month. We have previously identified a small population of colony-forming endometrial stromal cells which we hypothesize are mesenchymal stem cells (MSC). The aim of this study was to determine if the co-expression of two perivascular cell markers, CD146 and platelet-derived growth factor-receptor b (PDGF-Rb), will prospectively isolate endometrial stromal cells which exhibit MSC properties, and determine their location in human endometrium. METHODS: Single cell suspensions of human endometrial stromal cells were fluorescence activated cell sorting (FACS) sorted into CD146 1 PDGF-Rb 1 and CD146 2 PDGF-Rb 2 populations and analysed for colony-forming ability, in vitro differentiation and expression of typical MSC markers. Full thickness human endometrial sections were co-stained for CD146 and PDGF-Rb. RESULTS: FACS stromal CD146 1 PDGF-Rb 1 stromal cells (1.5% of sorted population) were enriched for colony-forming cells compared with CD146 2 PDGF-Rb 2 cells (7.7+1.7 versus 0.7+0.2% P< 0.0001), and also underwent differentiation into adipogenic, osteogenic, myogenic and chondrogenic lineages. They expressed MSC phenotypic surface markers and were located near blood vessels. CONCLUSION: This study shows that human endometrium contains a small population of MSC-like cells that may be responsible for its cyclical growth, and may provide a readily available source of MSC for tissue engineering applications.

504 citations


Cites background from "Clonogenic multipotent stem cells i..."

  • ...Slight expression of these two markers was observed in the undifferentiated cells, which has also been observed in adipose-derived MSC (Rodriguez et al., 2006)....

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Journal ArticleDOI
TL;DR: The current knowledge of the tissue localization of ASCs in situ, their characterization and heterogeneity in vitro, and the lack of standardization in isolation and culture methods are summarized and discussed.
Abstract: Adipose tissue as a stem cell source is ubiquitously available and has several advantages compared to other sources. It is easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose-derived mesenchymal stromal/stem cells (ASCs) yields a high amount of stem cells, which is essential for stem-cell-based therapies and tissue engineering. Several studies have provided evidence that ASCs in situ reside in a perivascular niche, whereas the exact localization of ASCs in native adipose tissue is still under debate. ASCs are isolated by their capacity to adhere to plastic. Nevertheless, recent isolation and culture techniques lack standardization. Cultured cells are characterized by their expression of characteristic markers and their capacity to differentiate into cells from meso-, ecto-, and entodermal lineages. ASCs possess a high plasticity and differentiate into various cell types, including adipocytes, osteoblasts, chondrocytes, myocytes, hepatocytes, neural cells, and endothelial and epithelial cells. Nevertheless, recent studies suggest that ASCs are a heterogeneous mixture of cells containing subpopulations of stem and more committed progenitor cells. This paper summarizes and discusses the current knowledge of the tissue localization of ASCs in situ, their characterization and heterogeneity in vitro, and the lack of standardization in isolation and culture methods.

419 citations


Cites background from "Clonogenic multipotent stem cells i..."

  • ...[95] L....

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  • ...Different studies described ASCs’ plasticity towards chondrocytes, osteoblasts, adipocytes, and myocytes (cardiomyocytes, smooth muscle, and skeletal muscle cells) [24, 36, 90–97]....

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  • ...The multilineage potential of ASCs has also been shown at the single cell level [29, 95, 122]....

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Journal ArticleDOI
TL;DR: This UCP1-TRAP data set demonstrates striking similarities and important differences between these cell types, including a smooth muscle-like signature expressed by beige, but not classical brown, adipocytes.

375 citations


Cites background from "Clonogenic multipotent stem cells i..."

  • ...In Vitro Conversion of SMCs into Adipocytes with a Thermogenic Gene Signature Some evidence indicates that a stem cell population in adipose tissues can differentiate into either SMCs or adipocytes (Rodrı́guez et al., 2006; Yin et al., 2012), but there are no investigations of a direct phenotypic switch between SMCs or SMC-like cells into adipocytes....

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  • ...…Thermogenic Gene Signature Some evidence indicates that a stem cell population in adipose tissues can differentiate into either SMCs or adipocytes (Rodrı́guez et al., 2006; Yin et al., 2012), but there are no investigations of a direct phenotypic switch between SMCs or SMC-like cells into…...

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Journal ArticleDOI
TL;DR: White adipose tissue-derived stem cells (ASCs) are capable of differentiating into numerous cell types of both mesodermal and nonmesodermal origin, leading to their extensive investigation from a therapeutic and tissue engineering perspective.

359 citations

References
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Journal ArticleDOI
TL;DR: The data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.
Abstract: Future cell-based therapies such as tissue engineering will benefit from a source of autologous pluripotent stem cells. For mesodermal tissue engineering, one such source of cells is the bone marrow stroma. The bone marrow compartment contains several cell populations, including mesenchymal stem cells (MSCs) that are capable of differentiating into adipogenic, osteogenic, chondrogenic, and myogenic cells. However, autologous bone marrow procurement has potential limitations. An alternate source of autologous adult stem cells that is obtainable in large quantities, under local anesthesia, with minimal discomfort would be advantageous. In this study, we determined if a population of stem cells could be isolated from human adipose tissue. Human adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), was processed to obtain a fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA cells can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of PLA cells are of mesodermal or mesenchymal origin with low levels of contaminating pericytes, endothelial cells, and smooth muscle cells. Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, the data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.

7,402 citations

Journal ArticleDOI
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.
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.

6,473 citations

Journal ArticleDOI
05 Apr 2001-Nature
TL;DR: It is indicated that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease.
Abstract: Myocardial infarction leads to loss of tissue and impairment of cardiac performance The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time1 Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation2,3,4,5; these events promote structural and functional repair6,7,8 This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice We sorted lineage-negative (Lin-) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein9 by fluorescence-activated cell sorting on the basis of c-kit expression10 Shortly after coronary ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the infarct Here we report that newly formed myocardium occupied 68% of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells The developing tissue comprised proliferating myocytes and vascular structures Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease

5,331 citations

Journal ArticleDOI
TL;DR: The isolation of stem cells from juvenile and adult rodent skin is described and it is proposed that these cells represent a novel multipotent adult stem cell and suggest that skin may provide an accessible, autologous source of stem cell for transplantation.
Abstract: We describe here the isolation of stem cells from juvenile and adult rodent skin. These cells derive from the dermis, and clones of individual cells can proliferate and differentiate in culture to produce neurons, glia, smooth muscle cells and adipocytes. Similar precursors that produce neuron-specific proteins upon differentiation can be isolated from adult human scalp. Because these cells (termed SKPs for skin-derived precursors) generate both neural and mesodermal progeny, we propose that they represent a novel multipotent adult stem cell and suggest that skin may provide an accessible, autologous source of stem cells for transplantation.

1,699 citations

Journal ArticleDOI
TL;DR: The data indicate the presence of a cell population within the SVF of human AT characterized as CD34+/CD31− exhibiting characteristics of endothelial progenitor cells, therefore, human AT might represent a source of stem/progenitor cells useful for cell therapy to improve vasculogenesis in adults.
Abstract: Background— Several studies have suggested that stem cells are present in the stroma-vascular fraction (SVF) of adipose tissue (AT). Methods and Results— To characterize the cell populations that compose the SVF of human AT originating from subcutaneous and visceral depots, fluorescence-activated cell sorter analysis was performed by use of fluorescent antibodies directed against the endothelial and stem cell markers CD31, CD34, CD133, and ABCG2. The freshly harvested SVF contained large numbers of CD34+ cells as well as cells expressing CD133 and ABCG2. Further analysis of the CD34+ cells revealed 2 CD34+ cell populations with differential expression of the endothelial cell marker CD31. Selection of the CD34+/CD31− cells by use of magnetic microbeads, followed by cell culture, demonstrated that this cell population could differentiate under appropriate conditions into endothelial cells. Moreover, in mouse ischemic hindlimb, intravenous injection of CD34+/CD31− cells was associated with an increase in the...

930 citations

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