Bone Marrow-Derived Mesenchymal Stromal Cells Express Cardiac-Specific Markers, Retain the Stromal Phenotype, and Do Not Become Functional Cardiomyocytes In Vitro

Rose, Robert A.; Jiang, Huijie; Wang, Xinghua; Helke, Simone; Tsoporis, James N.; Gong, Nanling; Keating, Stephanie; Parker, Thomas G.; Backx, Peter H.; Keating, Armand

doi:10.1634/stemcells.2008-0329

Cited by 196 publications

(145 citation statements)

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“…Consistent with recent findings [24,29], cells of the stem cell line used in this study were found to express mesenchymal stem cell markers, CD44, Stro-1, and vimentin ( Fig. 1B-1D; [30,31]) and to possess the capacity to differentiate into mesodermal cell types (Fig. 1E, 1F).…”

Section: Transplanted Adult Human Olfactory Stem Cells Are Mesenchymasupporting

confidence: 91%

“…Our in vitro characterization of the olfactory stem cells used in this study suggests that these cells are mesenchymal stem cells. The cells are immunopositive for the mesenchymal stem cell markers CD44, Stro-1, and vimentin [30,31] and are capable of differentiation into mesenchymal cell types (adipocytes and osteocytes). As Stro-1 is expressed exclusively in the lamina propria of the human olfactory mucosa [36], these cells appear to be similar to previously described populations of olfactory lamina propria-derived mesenchymal stem cells [24].…”

Section: Discussionmentioning

confidence: 99%

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Functional Effects of Adult Human Olfactory Stem Cells on Early-Onset Sensorineural Hearing Loss

et al. 2011

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Transplantation of exogenous stem cells has been proposed as a treatment to prevent or reverse sensorineural hearing loss. Here, we investigate the effects of transplantation of adult human olfactory mucosa-derived stem cells on auditory function in A/J mice, a strain exhibiting early-onset progressive sensorineural hearing loss. Recent evidence indicates that these stem cells exhibit multipotency in transplantation settings and may represent a subtype of mesenchymal stem cell. Olfactory stem cells were injected into the cochleae of A/J mice via a lateral wall cochleostomy during the time period in which hearing loss first becomes apparent. Changes in auditory function were assessed 1 month after transplantation and compared against animals that received sham injections. Hearing threshold levels in stem cell-transplanted mice were found to be significantly lower than those of sham-injected mice (p < .05) for both click and pure tone stimuli. Transplanted cells survived within the perilymphatic compartments but did not integrate into cochlear tissues. These results indicate that transplantation of adult human olfactory mucosa-derived stem cells can help preserve auditory function during early-onset progressive sensorineural hearing loss. STEM CELLS 2011;29:670-677 Disclosure of potential conflicts of interest is found at the end of this article.

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Section: Transplanted Adult Human Olfactory Stem Cells Are Mesenchymasupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Functional Effects of Adult Human Olfactory Stem Cells on Early-Onset Sensorineural Hearing Loss

et al. 2011

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“…The ultrastructural maturation in differentiated cardiomyocytes seemed more heterogeneous, and did not reach the fully mature adult phenotype during the observation period. Recently published data reported that murine MSCs inspite of expressing cardiac-specific markers do not become functional cardiomyocytes in vitro (Rose et al 2008). Our result also suggests that human bone marrow-derived MSCs follow a similar pattern in vitro and differentiate into cardiomyocytes with limited functional ability.…”

Section: Resultssupporting

confidence: 74%

Ischemic cardiac tissue conditioned media induced differentiation of human mesenchymal stem cells into early stage cardiomyocytes

et al. 2012

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Mesenchymal stem cells (MSCs) are multipotent, can be easily expanded in culture and hence are an attractive therapeutic tool for cardiac repair. MSCs have tremendous potential to transdifferentiate to cardiac lineage both in vitro and in vivo. The present study examined the differentiation capacity of conditioned media derived from ischemic cardiac tissue on human MSCs. Human Bone marrow-derived MSCs after due characterization by immunocytochemistry and flow cytometry for MSC specific markers were induced by culture media derived from ischemic (n = 13) and non-ischemic (n = 18) human cardiac tissue. Parallel cultures were treated with 5-azacytidine (5-azaC), a potent cardiomyogen. MSCs induced with ischemic conditioned media formed myotube like structures, expressed sarcomeric Troponin I, alpha myosin heavy chain proteins and were positive for cardiac specific markers (Nkx2.5, human atrial natriuretic peptide, myosin light chain-2a, GATA-4) as was observed in 5-azaC treated cells. However, uninduced MSCs as well as those induced with non-ischemic cardiac conditioned media still maintained the fibroblast morphology even after 3 weeks post-induction. Transmission electron microscopic studies of cardiomyocyte-like cells derived from MSCs revealed presence of sarcomeric bands but failed to show gap junctions and intercalated discs as of adult cardiomyocytes. These findings demonstrate that ischemic cardiac conditioned media induces morphological and molecular changes in MSCs with cardiac features, but at a primitive stage. Proteomics analysis of the ischemic conditioned media revealed differential expression of three relevant proteins (C-type lectin superfamily member 13, Testis-specific chromodomain protein Y2 and ADP/ATP translocase 1), whose exact role in cardiac regeneration needs further analysis.

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“…A recent study by Rose et al has shown that although bone marrow-derived MSCs can be induced to adopt a cardiac muscle phenotype, by expressing cardiac-specific makers, they still retain the MSC phenotype and fail to become functional cardiomyocytes in vitro [63]. The same may be the case here since PAX3-transduced hMSCs still maintain a MSC phenotype (Fig.…”

Section: Discussionsupporting

confidence: 55%

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

Gang

Darabi

Bosnakovski

et al. 2009

Experimental Cell Research

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Mesenchymal stem cell preparations have been proposed for muscle regeneration in musculoskeletal disorders. Although MSCs have great in vitro expansion potential and possess the ability to differentiate into several mesenchymal lineages, myogenesis has proven to be much more difficult to induce. We have recently demonstrated that Pax3, the master regulator of the embryonic myogenic program, enables the in vitro differentiation of a murine mesenchymal stem cell line (MSCB9-Pax3) into myogenic progenitors. Here we show that injection of these cells into cardiotoxin-injured muscles of immunodeficient mice leads to the development of muscle tumors, resembling rhabdomyosarcomas. We then extended these studies to primary human mesenchymal stem cells (hMSCs) isolated from bone marrow. Upon genetic modification with a lentiviral vector encoding PAX3, hMSCs activated the myogenic program as demonstrated by expression of myogenic regulatory factors. Upon transplantation, the PAX3-modified MSCs did not generate rhabdomyosarcomas but rather, resulted in donor-derived myofibers. These were found at higher frequency in PAX3-transduced hMSCs than in mock-transduced MSCs. Nonetheless, neither engraftment of PAX3-modified or unmodified MSCs resulted in improved contractility.Thus these findings suggest that limitations remain to be overcome before MSC preparations result in effective treatment for muscular dystrophies.

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Bone Marrow-Derived Mesenchymal Stromal Cells Express Cardiac-Specific Markers, Retain the Stromal Phenotype, and Do Not Become Functional Cardiomyocytes In Vitro

Cited by 196 publications

References 56 publications

Functional Effects of Adult Human Olfactory Stem Cells on Early-Onset Sensorineural Hearing Loss

Functional Effects of Adult Human Olfactory Stem Cells on Early-Onset Sensorineural Hearing Loss

Ischemic cardiac tissue conditioned media induced differentiation of human mesenchymal stem cells into early stage cardiomyocytes

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

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