Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell

Krause, Diane S.; Theise, Neil D.; Collector, Michael I.; Henegariu, Octavian; Hwang, Sun Jin; Gardner, Rebekah; Neutzel, Sara; Sharkis, Saul J.

doi:10.1016/s0092-8674(01)00328-2

Cited by 2,469 publications

(1,839 citation statements)

References 38 publications

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“…The self-renewal capacities of stromal keratocytes are poorly understood and the cell source is unclear so far. It is reported that BMderived stem cells, such as hematopoietic and mesenchymal stem cells, have tremendous differentiation capacity beyond their blastoderm (Gussoni et al, 1999;Krause et al, 2001;Jiang et al, 2002). Taken together, the present findings raise the possibility that the stem cells from the transplanted BM may transdifferentiate into corneal keratocytes and communicate with neighboring keratocytes, organizing themselves into a keratocyte cellular network in the corneal stroma.…”

Section: Discussionsupporting

confidence: 61%

Characteristic Morphology and Distribution of Bone Marrow Derived Cells in the Cornea

Takayama

Kondo

Kobayashi

et al. 2009

The Anatomical Record

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Enhanced green fluorescence protein (eGFP)-labeled bone marrow (BM) cells were transplanted into syngeneic C57BL/6 (wild-type) mice to investigate the distribution pattern, immunohistochemical characteristics, three-dimensional structure, and ultrastructure of the BM-derived cells in the mouse cornea using a fluorescence microscope, a confocal laser scanning microscope, and a transmission electron microscope. This study provided direct evidence that two morphologically distinct types of BMderived cells were distributed in the mouse cornea. The majority of the GFP(1) cells showed a flattened polygonal form with obtuse angles and these cells were distributed in the corneal stroma. The other type was the GFP(1) cells demonstrating slim cell bodies with long and extremely thin dendrites and which were distributed in the corneal epithelium. The immunohistochemical characteristics and ultrastructure of BM-derived cells suggest that most of these cells have a macrophage lineage, whereas some cells in the corneal stroma do not. Interestingly, the direct intimate contact between GFP-labeled BM derived cells and non-GFP-labeled resident cells within the corneal stroma were also clearly visualized at the fine structural level. These data provide new and more detailed insight into the nature of BM-derived cells in the cornea.

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Section: Discussionsupporting

confidence: 61%

Characteristic Morphology and Distribution of Bone Marrow Derived Cells in the Cornea

Takayama

Kondo

Kobayashi

et al. 2009

The Anatomical Record

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“…Immunohistochemistry staining was performed with specific antibodies against CD45, wheat germ agglutinin, α‐sarcomeric actin, BrdU , and IdU (Sigma). To assess the fate of the transplanted male CPCs, Y chromosome was detected by fluorescence in situ hybridization according to the modified manufacturer's protocol (ID Labs, London, ON) 3, 8, 13…”

Section: Methodsmentioning

confidence: 99%

Repeated Administrations of Cardiac Progenitor Cells Are Superior to a Single Administration of an Equivalent Cumulative Dose

Tang

Nakamura

et al. 2018

JAHA

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BackgroundWe have recently found that 3 repeated doses (12×106 each) of c‐kitPOS cardiac progenitor cells (CPCs) were markedly more effective than a single dose of 12×106 cells in alleviating postinfarction left ventricular dysfunction and remodeling. However, since the single‐dose group received only one third of the total number of CPCs given to the multiple‐dose group, it is unknown whether the superior therapeutic efficacy was caused by repeated treatments per se or by administration of a higher total number of CPCs. This issue has major clinical implications because multiple cell injections in patients pose significant challenges, which would be obviated by using 1 large injection. Accordingly, we determined whether the beneficial effects of 3 repeated CPC doses can be recapitulated by 1 large dose containing the same total number of cells.Methods and ResultsRats with a 30‐day‐old myocardial infarction received 3 echo‐guided intraventricular infusions, 35 days apart, of vehicle‐vehicle‐vehicle, 36×106 CPCs‐vehicle‐vehicle, or 3 equal doses of 12×106 CPCs. Infusion of a single, large dose of CPCs (36×106 cells) produced an initial improvement in left ventricular function, but no further improvement was observed after the second and third infusions (both vehicle). In contrast, each of the 3 doses of CPCs (12×106) caused a progressive improvement in left ventricular function, the cumulative magnitude of which was greater than with a single dose. Unlike the single dose, repeated doses reduced collagen content and immune cell infiltration.ConclusionsThree repeated doses of CPCs are superior to 1 dose even though the total number of cells infused is the same, possibly because of greater antifibrotic and anti‐inflammatory actions.

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“…Bone marrow mesenchymal stem cells (MSCs) are currently among the best characterized adult stem cells (Majumdar et al, 1998;Pittenger et al, 1999) isolated from various tissue sources such as fat, muscle, and bone (Jiang et al, 2002b;Sottile et al, 2002;Zuk et al, 2002). These cells are able to differentiate into bone, fat, cartilage, muscle tissue, and neurons (Mackay et al, 1998;Reyes et al, 2001;Sekiya et al, 2004;Woodbury et al, 2000) and were ultimately reported in almost all cell lineages (Jiang et al, 2002;Krause et al, 2001). For these reasons, the isolation and manipulation of adult stem cells represents a promising tool for understanding tissue development and regeneration, as well as for studying the engineered repair of tissues and organs (Orlic et al, 2001;Pittenger and Martin, 2004;Wakitani et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

Bosnakovski

Mizuno

Kim

et al. 2006

Biotech & Bioengineering

444

322

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Bone marrow mesenchymal stem cells (MSCs) are candidate cells for cartilage tissue engineering. This is due to their ability to undergo chondrogenic differentiation after extensive expansion in vitro and stimulation with various biomaterials in three-dimensional (3-D) systems. Collagen type II is one of the major components of the hyaline cartilage and plays a key role in maintaining chondrocyte function. This study aimed at analyzing the MSC chondrogenic response during culture in different types of extracellular matrix (ECM) with a focus on the influence of collagen type II on MSC chondrogenesis. Bovine MSCs were cultured in monolayer as well as in alginate and collagen type I and II hydrogels, in both serum free medium and medium supplemented with transforming growth factor (TGF) b1. Chondrogenic differentiation was detected after 3 days of culture in 3-D hydrogels, by examining the presence of glycosaminoglycan and newly synthesized collagen type II in the ECM. Differentiation was most prominent in cells cultured in collagen type II hydrogel, and it increased in a timedependent manner. The expression levels of the of chondrocyte specific genes: sox9, collagen type II, aggrecan, and COMP were measured by quantitative ''Real Time'' RT-PCR, and genes distribution in the hydrogel beads were localized by in situ hybridization. All genes were upregulated by the presence of collagen, particularly type II, in the ECM. Additionally, the chondrogenic influence of TGF b1 on MSCs cultured in collagenincorporated ECM was analyzed. TGF b1 and dexamethasone treatment in the presence of collagen type II provided more favorable conditions for expression of the chondrogenic phenotype. In this study, we demonstrated that collagen type II alone has the potential to induce and maintain MSC chondrogenesis, and prior interaction with TGF b1 to enhance the differentiation.

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Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell

Cited by 2,469 publications

References 38 publications

Characteristic Morphology and Distribution of Bone Marrow Derived Cells in the Cornea

Characteristic Morphology and Distribution of Bone Marrow Derived Cells in the Cornea

Repeated Administrations of Cardiac Progenitor Cells Are Superior to a Single Administration of an Equivalent Cumulative Dose

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

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