Enabling stem cell therapies through synthetic stem cell–niche engineering

Peerani, Raheem; Zandstra, Peter W.

doi:10.1172/jci41158

Cited by 159 publications

(131 citation statements)

References 132 publications

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“…Physiological microenvironments play a crucial role in maintenance of stem cell properties, and the oxygen concentration is an important component of the stem cell niche (Peerani and Zandstra 2010;Santilli et al 2010). In the present study, hypoxia provokes MSCs proliferation, and increases ALP activity and production of both Col I/III.…”

Section: Discussionsupporting

confidence: 51%

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Huang

Deng

Wang

et al. 2011

Tohoku J. Exp. Med.

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Mesenchymal stem sells (MSCs) have received much attention in the field of bone tissue engineering due to their biological capability to differentiate into osteogenic lineage cells. Hypoxia-inducible factor 1alpha (HIF-1α) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfα1) is a transcription regulator that is involved in the chondrocyte differentiation and ossification. In the present study, we investigated the effects of hypoxia on biological capability of MSCs. MSCs were isolated from adult rabbit bone marrow, and were cultured in vitro under normoxia (air with 5% CO 2 ) or hypoxia (5% CO 2 and 95% N 2 ). The proliferation of MSCs, alkaline phosphatase (ALP) activity, and production of collagens type I and type III (Col I/III) were examined. The expression levels of HIF-1α and Cbfα1 were measured by real-time PCR and western blot analyses. We found that hypoxia significantly induced the proliferation of MSCs and increased ALP activity and the production of Col I/III. Moreover, hypoxia increased the expression of Cbfα1 mRNA after 12 h, whereas the expression of HIF-1α mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1α expression with a small interfering RNA significantly increased the expression levels of Cbfα1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfα1 may be negatively regulated by HIF-1α.

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Section: Discussionsupporting

confidence: 51%

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Huang

Deng

Wang

et al. 2011

Tohoku J. Exp. Med.

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“…20) The ECM affects growth and differentiation of stem cells; it is one of the important components that contributes to the stem cell niche (a static microenvironment into which stem cells and progenitor cells are nested). 21,22) In the heart, the ECM network provides support for myocardial cell contraction and is responsible for the distribution of mechanical forces and signal transduction to individual cells throughout the myocardium via cell . Glucose consumption and lactic acid production ratios.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Fibroblast-Derived Extracellular Matrix Produced <I>In Vitro</I> Stimulates Growth and Metabolism of Cultured Ventricular Cells

et al. 2013

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SummaryCardiac fi broblasts (CFs) produce extracellular matrix (ECM) which is a potent regulator of heart cell function and growth, and provides a supportive microenvironment for heart cells. Therefore, CF-derived ECM produced in vitro is very suitable for heart-cell culturing and cardiac tissue engineering. The aim of this study was to investigate the effect of CF-derived ECM produced in vitro on the growth and metabolism of cultured ventricular cells. CF-derived ECM-coated cell culture dishes were prepared by culturing rat CFs and then decellularizing the cultures. Isolated neonatal rat ventricular cells were seeded on ECM-coated, collagen I-coated or uncoated dishes, and the growth of cells after 1-5 days of culture was assayed with MTT reagent. In addition, cellular metabolic activity was analyzed by spectrophotometric methods and protein levels of sarco(endo)plasmic reticulum Ca 2+ -ATPase type 2a (SERCA2a) by Western blotting. The relative growth of ventricular cells was better on ECM-coated than on uncoated or collagen I-coated dishes. Furthermore, the glucose consumption ratio, lactic acid production ratio, Na + /K + -ATPase activity, SERCA activity and protein levels of SERCA2a were all higher in cells on the ECM-coated dishes. In conclusion, cardiac fi broblast-derived ECM produced in vitro stimulates the growth and metabolism of cultured ventricular cells. This study indicates that the bioactivity of the ECM supports heart cell growth in vitro, and this might be useful for cardiac tissue engineering. (Int Heart J 2013; 54: 40-44)

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“…The combination of biomaterials with cell-based therapies leads to a positive direction in the treatment of such disabling degenerative senile diseases [46]. For skin regeneration purposes three dimensional stem cell cultures are being established and their three dimensional printing to generate stem cell microenvironment engineered models are being used [47].…”

Section: Future Perspectivesmentioning

confidence: 99%

Stem Cells in Regenerative Medicine: Prospects and Pitfalls

Zehravi¹,

Shahid²,

Kashmala³

et al. 2017

Natl. j. health sci.

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Stem cells are the cells that have the ability to regenerate themselves and are able to differentiate into one or more specialized cell types. This unique property makes them a valuable source for in vitro disease modeling, drug designing, regenerative medicine and tissue engineering. As no specie can fully mimic the human microenvironment, human cell models derived from patients cells provide a fascinating avenue for enhancing our current understanding of the early molecular stages of various diseases followed by validating therapeutics. In this paper, we reviewed the role of stem cells in regenerative medicine that includes use of cord blood derived stem cells in medicine and patient specific induced pluripotent stem cells for future transplant purposes and the hurdles and obstacles that we need to address before we can safely use these cells for patient cure.

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Enabling stem cell therapies through synthetic stem cell–niche engineering

Cited by 159 publications

References 132 publications

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Cardiac Fibroblast-Derived Extracellular Matrix Produced <I>In Vitro</I> Stimulates Growth and Metabolism of Cultured Ventricular Cells

Stem Cells in Regenerative Medicine: Prospects and Pitfalls

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