Isolation and Characterization of Size‐Sieved Stem Cells from Human Bone Marrow

Hung, Shih Chieh; Chen, Nien Jung; Hsieh, Shie Liang; Li, Hung; Li, Hsiao; Lo, Wai‐Hee

doi:10.1634/stemcells.20-3-249

Cited by 250 publications

(189 citation statements)

References 43 publications

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“…We have previously investigated the signaling pathways involved in chondrogenesis under the control of type I and type II collagen, TGF␤1, and platelet-rich plasma (3,4,32,33,38). Building on the observations from our previous studies, we established a coculture system in which MSCs were directed toward chondrogenesis under the influence of mature chondrocytes, thereby creating a better simulation of physiologic conditions.…”

Section: Discussionmentioning

confidence: 99%

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In vitro stage‐specific chondrogenesis of mesenchymal stem cells committed to chondrocytes

Chen

Lai

et al. 2009

Arthritis & Rheumatism

110

118

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Objective. Osteoarthritis is characterized by an imbalance in cartilage homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC)-based therapies. However, in vivo implantation of undifferentiated MSCs has led to unexpected results. This study was undertaken to establish a model for preconditioning of MSCs toward chondrogenesis as a more effective clinical tool for cartilage regeneration.Methods. A coculture preconditioning system was used to improve the chondrogenic potential of human MSCs and to study the detailed stages of chondrogenesis of MSCs, using a human MSC line, Kp-hMSC, in commitment cocultures with a human chondrocyte line, hPi (labeled with green fluorescent protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold and analyzed for their neocartilage-forming ability.Results. Coculture of hPi-GFP chondrocytes with Kp-hMSCs induced chondrogenesis, as indicated by the increased expression of chondrogenic genes and accumulation of chondrogenic matrix, but with no effect on osteogenic markers. The chondrogenic process of committed MSCs was initiated with highly activated chondrogenic adhesion molecules and stimulated cartilage developmental growth factors, including members of the transforming growth factor ␤ superfamily and their downstream regulators, the Smads, as well as endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and vascular endothelial growth factor. Furthermore, committed Kp-hMSCs acquired neocartilageforming potential within the collagen scaffold. Osteoarthritis (OA), one of the most common musculoskeletal diseases, has been ascribed to an imbalance in cartilage homeostasis in the aging process (1,2). Hyaline cartilage has little capacity for self-repair. As a result, continuous mechanical stress can lead to the degradation of articular cartilage, culminating in a vicious cycle of destructive processes (3). Many therapeutic interventions directed at the restoration of the reparative capacity of chondrocytes have been explored (3-5). One of the emerging approaches is cell-based therapy, in which expanded chondrocytes are used for cartilage repair. However, the outcome of this approach has been disappointing, due to the difficulties in maintaining chondrocytic phenotypes and the decrease in proliferative capacity of autologous chondrocytes with increasing age (1,6,7). Conclusion. These findings help define the molecular markers of chondrogenesis and more accuratelyCell therapy based on autologous mesenchymal stem cells (MSCs), which have a vast proliferative ca-

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Section: Discussionmentioning

confidence: 99%

“…We have previously investigated the methods of purification, characterization, differentiation, and application of multipotent MSCs (10,(32)(33)(34)(35). We have also studied the expression of matrix proteins, the type I and type II collagens, which induce chondrogenesis in human MSCs under the influence of TGF␤1 (3).…”

mentioning

confidence: 99%

In vitro stage‐specific chondrogenesis of mesenchymal stem cells committed to chondrocytes

Chen

Lai

et al. 2009

Arthritis & Rheumatism

110

118

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“…In addition, several other studies provided direct evidence that BM stem cells are heterogenous and perhaps pluripotent. [84][85][86][87] For example, BM was found to contain endothelial-, 26 bone-, 31,88 skeletal muscles- 34 and cardiac-TCSC. 38 Interestingly, those endothelial-, skeletal muscle and cardiac-TSC were found to be CXCR4 þ CD45 À .…”

Section: Heterogenous Populations Of Stem Cells In Bone Marrow M Kucimentioning

confidence: 99%

“…Such a possibility was suggested in a recently published report. 87,[108][109][110] Mankind is searching for a key to longevity and there is no doubt that stem cells could be an important answer to this problem. Thus, there is a need for a reliable source of stem cells and adult TCSC could potentially provide a real-therapeutic alternative for embryonic stem (ES) cells and therapeutic cloning.…”

Section: Therapeutic Implications For Tcscmentioning

confidence: 99%

Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells

et al. 2005

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Evidence is presented that bone marrow (BM) in addition to CD45 positive hematopoietic stem cells contains a rare population of heterogenous CD45 negative nonhematopoietic tissue committed stem cells (TCSC). These nonhematopoietic TCSC (i) are enriched in population of CXCR4 þ CD34 þ AC133 þ lin À CD45 À and CXCR4 þ Sca-1 þ lin À CD45 À in humans and mice, respectively, (ii) display several markers of pluripotent stem cells (PSC) and (iii) as we envision are deposited in BM early in development. Thus, since BM contains versatile nonhematopoietic stem cells, previous studies on plasticity trans-dedifferentiation of BM-derived hematopoietic stem cells (HSC) that did not include proper controls to exclude this possibility could lead to wrong interpretations. Therefore, in this spotlight review we present this alternative explanation of 'plasticity' of BMderived stem cells based on the assumption that BM stem cells are heterogenous. We also discuss a potential relationship of TCSC/PSC identified by us with other BM-derived CD45 negative nonhematopoietic stem cells that were recently identified by other investigators (eg MSC, MAPC, USSC and MIAMI cells). Finally, we discuss perspectives and pitfalls in potential application of these cells in regenerative medicine.

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“…However, STRO-1 antigen is progressively lost in culture (30). Additionally, in some reported studies, bone marrow-derived MSCs had negative (31) or only dimly positive (14) expression of STRO-1. With regard to MSCs derived from locations other than the bone marrow, Gronthos and colleagues reported that STRO-1 antigen was not detected in human adipose tissue-derived stromal cells in contrast to findings in human bone marrow-derived stromal cells (10), although Zuk et al reported that the rate of expression of STRO-1 was 31% in adipose tissue-derived MSCs (8).…”

mentioning

confidence: 97%

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

Sakaguchi¹,

Sekiya²,

Yagishita³

et al. 2005

Arthritis & Rheumatism

1,375

1,171

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Objective. To compare the properties of human mesenchymal stem cells (MSCs) isolated from bone marrow, synovium, periosteum, skeletal muscle, and adipose tissue.Methods. Human mesenchymal tissues were obtained from 8 donors during knee surgery for ligament injury. After collagenase digestion or gradient-density separation, nucleated cells were plated at an appropriate density for expansion at the maximum rate without colony-to-colony contact. Yield, expandability, differentiation potential, and epitope profile were compared among MSCs from the 5 different tissue sources.Results. Colony number per 10 3 nucleated cells was lower, and cell number per colony was higher, in bone marrow than in other mesenchymal tissues. When the cells were replated at low density every 14 days, bone marrow-, synovium-, and periosteum-derived cells retained their proliferation ability even at passage 10. In chondrogenesis studies in which the cells were pelleted and cultured in vitro, pellets from bone marrow-, synovium-, and periosteum-derived cells were shown to be larger and stained more extensively for cartilage matrix. Synovium-derived cells, in particular, had the greatest ability for chondrogenesis. In adipogenesis experiments, the frequency of oil red O-positive colonies was highest in synovium-and adipose tissue-derived cells. In studies of osteogenesis, the rate of alizarin red-positive colonies was highest in bone marrow-, synovium-, and periosteum-derived cells. For epitope profiling, 15 surface antigens were measured. Most appeared to have similar epitope profiles irrespective of cell source.Conclusion. Our findings indicate that there are significant differences in MSC properties according to tissue source, beyond donor and experimental variation. Superiority of synovium as a potential source of MSCs for clinical applications was demonstrated.

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Isolation and Characterization of Size‐Sieved Stem Cells from Human Bone Marrow

Abstract: ABSTRACT

Cited by 250 publications

References 43 publications

In vitro stage‐specific chondrogenesis of mesenchymal stem cells committed to chondrocytes

In vitro stage‐specific chondrogenesis of mesenchymal stem cells committed to chondrocytes

Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

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