Cytogenetic analysis of human bone marrow‐derived mesenchymal stem cells passaged <i>in vitro</i>

Zhang, Zhenxing; Guan, Lina; Zhang, Kun; Wang, Shouxian; Cao, Peicheng; Wang, Yonghe; Wang, Zhe; Dai, Long‐Jun

doi:10.1016/j.cellbi.2006.11.025

Cited by 74 publications

(68 citation statements)

References 10 publications

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“…The age of the donors included in our study ranged from 21-86 years. These observations are in agreement with data from other investigators, [21][22][23]34,35 who reported normal diploid karyotype without aneuploidy or polyploidy in MSCs from healthy donors or patients with no hematopoietic disorders.…”

Section: Discussionsupporting

confidence: 93%

Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts

Blau

Baldus

Hofmann

et al. 2011

Blood

162

132

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Section: Discussionsupporting

confidence: 93%

Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts

Blau

Baldus

Hofmann

et al. 2011

Blood

162

132

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“…The use of MSCs for therapeutic applications is based on their subsequent large-scale in vitro expansion, which may lead to genetic and epigenetic instabilities; however, up to now, data on MSC transformation are very few (Rubio et al,2005), showing normal karyotypes and DNA copy numbers in long-term culture (Rubio et al,2005;Zhang et al, 2007;. Telomeric deletions have been reported (Meza-Zepeda et al,2008), indicating that chromosomal aberrations may occur, but with a very low incidence .…”

Section: Methylation Changes During Bone Marrow Msc Culture: What Liementioning

confidence: 99%

From bone marrow to therapeutic applications: different behaviour and genetic/epigenetic stability during mesenchymal stem cell expansion in autologous and foetal bovine sera?

Tonti¹,

Mannello²

2008

Int. J. Dev. Biol.

107

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Bone marrow-derived mesenchymal stem cells are a multipotent adult cellular population endowed with broad differentiation potential. Their regeneration capability, ease to undergo gene modifications, and immuno-suppressive capacity makes them optimal tools for tissue engineering, gene-and immuno-therapy. Due to the ever-increasing number of studies on the clinical applications of mesenchymal stem cells in regenerative medicine, these cells have become attractive targets in clinical transplantation. However, the identification and definition of mesenchymal stem cell culture media for their clinical application in cell therapy is currently a matter of strong discussion. Up to now, clinical studies have been conducted with mesenchymal stem cells cultured in foetal calf serum, and the chance of contamination or immunological reaction towards xenogeneic compounds must be taken into consideration. On the other hand, a serum-free medium without the addition of growth factors is not able to expand these cells in vitro; so the evaluation of which is best, among foetal calf serum, human serum (whether autologous or allogeneic) and platelet-rich plasma, is a "hot topic" urgently needing further research efforts. The need for the establishment of standardized protocols for mesenchymal stem cell preparations, in order not to interfere with their self-renewal and differentiation processes, assuring durable engraftment and long-term therapeutic effects, is evidently crucial. Therefore, the search for optimal culture conditions for the effective clinical-scale production of vast numbers of mesenchymal stem cells for cellular therapy is of paramount importance and the need for a robust passage from basic to translational research is fundamental. KEY WORDS: AB serum, autologous serum, mesenchymal stem cell, platelet-rich medium The starting pointThe first isolation of fibroblast-like colonies from bone marrow falls back to 1970, when Friedenstein reported the isolation of marrow-derived fibroblast-like cells, able to adhere to the plastic substrate of the cell culture plate (Friedenstein et al., 1970). On this basis, many approaches have been investigated and several protocols have been established to prepare primary cultures of bone marrow-derived mesenchymal stem cells (MSC) with more homogeneous cell population (Pittenger et al., 1999;Jiang et al., 2002). These MSCs are defined as self-renewable, multipotent progenitor cells with the capacity to differentiate into lineagespecific cells that form bone, cartilage, fat, tendon and muscle Int. J. Dev. Biol. 52: 1023-1032 (2008) tissue; in addition to the capacity to differentiate into their natural derivatives, MSCs have the capability to differentiate into other types of cells, giving rise to hepatic, renal, cardiac and neural cells (Song and Tuan, 2004;Pansky et al., 2007). Moreover, MSCs have been isolated not only from bone marrow, but also from other tissues such as adipose tissue, skeletal muscle, trabecular bone, liver, brain, placenta, deciduous teeth, pancrea...

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“…To the best of our knowledge, there are no studies describing methylationsilencing mechanisms for Alk receptors in vitro, but epigenetic changes during ex vivo expansion (including methylation) have been described for mesenchymal stem cells (MSCs). Choi et al showed how MSCs from late passages increased their methylation state in genes related to DNA replication, cell cycle and adipogenic differentiation [26,27]. We can suggest that the changes occurring during expansion and prior to cell therapy applications may have special relevance for the final behavior of cells.…”

Section: Discussionmentioning

confidence: 81%

The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

Sanz-Ramos

Dotor²,

Izal-Azcárate

2014

Cellular and Molecular Biology Letters

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Abbreviations used: Alk-1 -activin receptor-like kinase 1; Alk-5 -activin receptor-like kinase 5; FGFR3 -fibroblast growth factor receptor 3; FA -focal adhesions; MSCsmesenchymal stem cells; OA -osteoarthritis; TGFβ -transforming growth factor β; Col2 -type II collagen; Col1 -type I collagen; Col10 -type X collagen Abstract: We aim to demonstrate the role of Alk receptors in the response of hydrogel expansion. Chondrocytes from rat knees were cultured onto plastic and hydrogel surfaces. Alk-1 and Alk-5 were overexpressed or silenced and the effects on cells during expansion were tested and confirmed using peptide inhibitors for TGFβ. Overexpression of Alk-5 and silencing of Alk-1 led to a loss of the chondrocyte phenotype, proving that they are key regulators of chondrocyte mechanosensing. An analysis of the gene expression profile during the expansion of these modified cartilage cells in plastic showed a better maintenance of the chondrocyte phenotype, at least during the first passages. These passages were also assayed in a mouse model of intramuscular chondrogenesis. Our findings indicate that these two receptors are important mediators in the response of chondrocytes to changes in the mechanical environment, making them suitable targets for modulating chondrogenesis. Inhibition of TGFβ could also be effective in improving chondrocyte activity in aged or expanded cells that overexpress Alk-1.

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Cytogenetic analysis of human bone marrow‐derived mesenchymal stem cells passaged in vitro

Cited by 74 publications

References 10 publications

Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts

Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts

From bone marrow to therapeutic applications: different behaviour and genetic/epigenetic stability during mesenchymal stem cell expansion in autologous and foetal bovine sera?

The role of Alk-1 and Alk-5 in the mechanosensing of chondrocytes

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