Over expression of HIF-1α in human mesenchymal stem cells increases their supportive functions for hematopoietic stem cells in an experimental co-culture model

Kiani, Ali Asghar; Abdi, Jahangir; Halabian, Raheleh; Roudkenar, Mehryar Habibi; Amirizadeh, Naser; Soltanpour, Mohammad Soleiman; Kazemi, Ahmad

doi:10.1179/1607845413y.0000000093

Cited by 19 publications

(21 citation statements)

References 39 publications

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“…Genetic manipulation promotes the viability of stem cell engraftment by overexpression of cytoprotective genes. The common overexpressed genes in promoting the survival of mesenchymal stem cells (MSCs) include v-Akt Murine Thymoma Viral Oncogene (AKT) [10], B-cell lymphoma 2 (Bcl-2) [11], heat shock protein 20 (Hsp20) [12], nuclear factor related (erythroid-derived 2)-like 2 (Nrf2) [13], heme oxygenase-1 (HO) [14,15], endothelial nitric oxide synthase (eNOS) [16], connexin 43 (Cx43) [17], and hypoxia inducible factor-1α (HIF-1α) [18]. Other overexpressed genes, such as wild-type p53 inducible phosphatase-1 (WIP-1) [19] and lipocalin 2 (Lcn2) [20], could decrease MSC senescence during the process.…”

Section: Introductionmentioning

confidence: 99%

Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

Pei

2017

Biomaterials

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Adult stem cells are a promising cell source for cartilage regeneration. Unfortunately, due to donor age and ex vivo expansion, stem cell senescence becomes a huge hurdle for these cells to be used clinically. Increasing evidence indicates that environmental preconditioning is a powerful approach in promoting stem cells’ ability to resist a harsh environment post-engraftment, such as hypoxia and inflammation. However, few reports organize and evaluate the literature regarding the rejuvenation effect of environmental preconditioning on stem cell proliferation and chondrogenic differentiation capacity, which are important variables for stem cell based tissue regeneration. This report aims to identify several critical environmental factors such as oxygen concentration, growth factors, and extracellular matrix and to discuss their preconditioning influence on stem cells’ rejuvenation including proliferation and chondrogenic potential as well as underlying molecular mechanisms. We believe that environmental preconditioning based rejuvenation is a simpler and safer strategy to program pre-engraftment stem cells for better survival and enhanced proliferation and differentiation capacity without the undesired effects of some treatments, such as genetic manipulation.

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Section: Introductionmentioning

confidence: 99%

Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

Pei

2017

Biomaterials

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“…The MSCs-HIF-1α are resistant against hypoxic, oxidative, and serumdeprived stress conditions (Kiani et al 2014).…”

Section: Genetic Manipulationmentioning

confidence: 99%

In vitro augmentation of mesenchymal stem cells viability in stressful microenvironments

Amiri

Jahanian-Najafabadi

Roudkenar

2015

Cell Stress and Chaperones

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Mesenchymal stem cells (MSCs) are under intensive investigation for use in cell-based therapies because their differentiation abilities, immunomodulatory effects, and homing properties offer potential for significantly augmenting regenerative capacity of many tissues. Nevertheless, major impediments to their therapeutic application, such as low proliferation and survival rates remain as obstacles to broad clinical use of MSCs. Another major challenge to evolution of MSC-based therapies is functional degradation of these cells as a result of their exposure to oxidative stressors during isolation. Indeed, oxidative stress-mediated MSC depletion occurs due to inflammatory processes associated with chemotherapy, radiotherapy, and expression of pro-apoptotic factors, and the microenvironment of damaged tissue in patients receiving MSC therapy is typically therapeutic not favorable to their survival. For this reason, any strategies that enhance the viability and proliferative capacity of MSCs associated with their therapeutic use are of great value. Here, recent strategies used by various researchers to improve MSC allograft function are reviewed, with particular focus on in vitro conditioning of MSCs in preparation for clinical application. Preconditioning, genetic manipulation, and optimization of MSC culture conditions are some examples of the methodologies described in the present article, along with novel strategies such as treatment of MSCs with secretome and MSC-derived microvesicles. This topic material is likely to find value as a guide for both research and clinical use of MSC allografts and for improvement of the value that use of these cells brings to health care.

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“…This study therefore suggested that the HSC niche microenvironment requires Hif‐2α to sustain normal hematopoiesis although the contribution of Hif‐2α deficiency in other tissues (i.e., tissues outside the BM) of Hif‐2α‐null recipient mice to the observed phenotype cannot be excluded. These genetic data, together with the observations that Hif‐1α and Hif‐2α regulate functions of endothelial cells , mesenchymal stem cells , and osteoblasts , all of which constitute HSC niches, imply that Hif‐dependent hypoxia signaling plays important roles in the BM microenvironment. Conditional deletion of Hif‐1α and Hif‐2α in functionally distinct niches, as it has been recently performed for other essential niche factors , will be the key to the understanding of Hif signaling in different HSC niches and its impact on HSCs and primitive progenitor cells.…”

Section: Hif Signaling In the Hsc Microenvironmentmentioning

confidence: 89%

Concise Review: Genetic Dissection of Hypoxia Signaling Pathways in Normal and Leukemic Stem Cells

et al. 2014

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Adult hematopoiesis depends on rare multipotent hematopoietic stem cells (HSCs) that selfrenew and give rise to progenitor cells, which differentiate to all blood lineages. The strict regulation of the fine balance between self-renewal and differentiation is essential for normal hematopoiesis and suppression of leukemia development. HSCs and progenitor cells are commonly assumed to reside within the hypoxic BM microenvironment, however, there is no direct evidence supporting this notion. Nevertheless, HSCs and progenitors do exhibit a hypoxic profile and strongly express Hif-1a. Although hypoxia signaling pathways are thought to play important roles in adult HSC maintenance and leukemogenesis, the precise function of Hif-dependent signaling in HSCs remains to be uncovered. Here we discuss recent gain-of-function and loss-offunction studies that shed light on the complex roles of hypoxia-signaling pathways in HSCs and their niches in normal and malignant hematopoiesis. Importantly, we comment on the current and often contrasting interpretations of the role of Hif-dependent signaling in stem cell functions.

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Over expression of HIF-1α in human mesenchymal stem cells increases their supportive functions for hematopoietic stem cells in an experimental co-culture model

Cited by 19 publications

References 39 publications

Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

In vitro augmentation of mesenchymal stem cells viability in stressful microenvironments

Concise Review: Genetic Dissection of Hypoxia Signaling Pathways in Normal and Leukemic Stem Cells

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