Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells

Grayson, Warren L.; Zhao, Feng; Bunnell, Bruce A.; Ma, Teng

doi:10.1016/j.bbrc.2007.05.054

Cited by 461 publications

(418 citation statements)

References 26 publications

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“…During in vitro culture, hDSPCs, which exhibited stem celllike characteristics in our previous study, gradually lose the expression of transcription factors associated with multipotency and self-renewal, such as SOX2 and NANOG for maintaining the characteristics of stem cells. Several previous reports suggested that the quality of the stem cells strongly depend on the culture method (Driskell et al, 2012;Grayson et al, 2007;Kuroda et al, 2010;Minchenko et al, 1994;Reiter et al, 2008;Ren et al, 2006;Rendl et al, 2005). Thus, we investigated whether hDSPCs retain their stemness in various culture conditions despite long-term culture.…”

Section: Discussionmentioning

confidence: 92%

“…It regulates various cellular events critical to the in vitro growth of cells. In the previous studies, hypoxia enhances the stemness of bone marrow mesenchymal stem cells (Grayson et al, 2007;Ren et al, 2006). Thus, we examined whether O 2 concentration had effects on preserving the stemness of hDSPCs.…”

Section: Discussionmentioning

confidence: 93%

“…Recent reports suggested that hypoxia contributes to maintain the stemness of MSCs (Grayson et al, 2007;Ren et al, 2006). Thus, we tested the effects of oxygen level on dermal progenitor markers and found that there were no significant differences between normoxic (20% of O 2 ) and hypoxic (1% or 5% of O 2 ) conditions in the mRNA expression levels of SOX2, NANOG and S100B (Supplementary Figs.…”

Section: Effects Of Oxygen In Maintaining the Stemness Of Hdspcsmentioning

confidence: 99%

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Novel In Vitro Culture Condition Improves the Stemness of Human Dermal Stem/Progenitor Cells

Shim

Lee

Shin

2013

Molecules and Cells

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Cell therapy using adult stem cells has emerged as a potentially new approach for the treatment of various diseases. Therefore, it is an essential procedure to maintain the stemness of adult stem cells for clinical treatment. We previously reported that human dermal stem/progenitor cells (hDSPCs) can be enriched using collagen type IV. However, hDSPCs gradually lose their stem cell properties as in vitro passages continue. In the present study, we developed optimized in vitro culture condition to improve the stemness of these hDSPCs. To evaluate whether the stemness of hDSPCs is well sustained in various culture conditions, we measured the expression levels of SOX2, NANOG, and S100B, which are well-known representative dermal progenitor markers. We observed that hDSPCs grown in three-dimensional (3D) culture condition had higher expression levels of those markers compared with hDSPCs grown in two-dimensional (2D) culture condition. Under the 3D culture condition, we further demonstrated that a high glucose (4.5 g/L) concentration enhanced the expression levels of the dermal progenitor markers, whereas O 2 concentration did not affect. We also found that skin-derived precursor (SKP) culture medium was the most effective, among various culture media, in increasing the dermal progenitor marker expression. We finally demonstrated that this optimized culture condition enhanced the expression level of human telomerase reverse transcriptase (hTERT), the proliferation, and the multipotency of hDSPCs, an important characteristic of stem cells. Taken together, these results suggested that this novel in vitro culture condition improves the stemness of hDSPCs.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 93%

Section: Effects Of Oxygen In Maintaining the Stemness Of Hdspcsmentioning

confidence: 99%

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Novel In Vitro Culture Condition Improves the Stemness of Human Dermal Stem/Progenitor Cells

Shim

Lee

Shin

2013

Molecules and Cells

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“…Thus, oxygen tension during in vitro expansion of MSCs might play a crucial regulatory role in the maintenance of stem cell properties. Recent studies show that the proliferation, differentiation, and survival of MSCs are affected by culture under low oxygen tension (MartinRendon et al 2007;Grayson et al 2007;Holzwarth et al 2010;Annabi et al 2003). However, the degree and duration of hypoxia described in previous studies vary greatly and may account, in part, for the conflicting effects of hypoxia on the proliferation and differentiation capacities of MSCs (Holzwarth et al 2010;Salim et al 2004;Lennon et al 2001;Malladi et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells

Kim

Lee

et al. 2016

Cell Stress and Chaperones

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Culture of mesenchymal stem cells (MSCs) under ambient conditions does not replicate the low oxygen environment of normal physiological or pathological states and can result in cellular impairment during culture. To overcome these limitations, we explored the effect of hypoxia (1 % O 2 ) on the biological characteristics of MSCs over the course of different culture periods. The following biological characteristics were examined in human bone marrow-derived MSCs cultured under hypoxia for 8 weeks: proliferation rate, morphology, cell size, senescence, immunophenotypic characteristics, and the expression levels of stemness-associated factors and cytokine and chemokine genes. MSCs cultured under hypoxia for approximately 2 weeks showed increased proliferation and viability. During long-term culture, hypoxia delayed phenotypic changes in MSCs, such as increased cell volume, altered morphology, and the expression of senescence-associated-β-gal, without altering their characteristic immunophenotypic characteristics. Furthermore, hypoxia increased the expression of stemness and chemokine-related genes, including OCT4 and CXCR7, and did not decrease the expression of KLF4, C-MYC, CCL2, CXCL9, CXCL10, and CXCR4 compared with levels in cells cultured under normoxia. In conclusion, low oxygen tension improved the biological characteristics of MSCs during ex vivo expansion. These data suggest that hypoxic culture could be a useful method for increasing the efficacy of MSC cell therapies.

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“…See, for instances, the papers of Heo et al [20], Eiselleova et al [21], Chung et al [22], and Schuldiner et al [23]. More generally, other conditions such as the level of oxygen, or of nutrients such as glucose, can also affect the growth of stem cells, as demonstrated in works such as [24,25,26]. Multivariable versions of the hyperbolastic growth models have been developed and applied in other works, and in a future work we plan to return to explore the issue of a multivariable model for stem cell growth that will aid researchers in measuring the effects of cytokines, oxygen, and other factors on the rate of proliferation.…”

Section: Modeling Proliferative Index Of Mesenchymal Stem Cellsmentioning

confidence: 99%

Mathematical modeling of stem cell proliferation

Tabatabai

Bursac

Eby

et al. 2010

Med Biol Eng Comput

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Abstract.The mathematical models prevalently used to represent stem cell proliferation do not have the level of accuracy that might be desired. The hyperbolastic growth models promise a greater degree of precision in representing data of stem cell proliferation. The hyperbolastic growth model H3 is applied to experimental data in both embryonic stem cells and adult mesenchymal stem cells. In the embryonic stem cells the results are compared with other popular models, including the Deasy model, which is used prevalently for stem cell growth. In the case of modelling adult mesenchymal stem cells, H3 is also successfully applied to describe the proliferative index. We demonstrated that H3 can accurately represent the dynamics of stem cell proliferation for both embryonic and adult mesenchymnal stem cells. We also recognize the importance of additional factors, such as cytokines, in determining the rate of growth. We propose the question of how to extend H3 to a multivariable model that can include the influence of growth factors.

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Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells

Cited by 461 publications

References 26 publications

Novel In Vitro Culture Condition Improves the Stemness of Human Dermal Stem/Progenitor Cells

Novel In Vitro Culture Condition Improves the Stemness of Human Dermal Stem/Progenitor Cells

Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells

Mathematical modeling of stem cell proliferation

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