scholarly journals Hypoxia-based Stem/Progenitor Cell Therapy: Focus on CXCR4/SDF-1 Axis

2017 ◽  
Vol 3 ◽  
pp. 64
Author(s):  
Asieh Heirani-Tabasi ◽  
Shirin Hamedakbari Toosi ◽  
Mahdi Mirahmadi ◽  
Mahmood Raeesolmohaddeseen

Cell therapy is becoming a promising approach to treat degenerative diseases. Homing of the transplanted cells is one of the continuous challenges being faced by the stem cell biologists. Chemokine receptors are one of the highly studied factors which are known to be crucial in controlling the cell/stem cell migration and targeted homing to the damaged tissues. The expression of chemokine receptors is dependent on a number of transcription factors and HIF-1α has been considered the crucial molecules controlling cellular migration and homing. Several studies have revealed that hypoxia conditions stabilize the HIF-1α which upregulate the CXCR4/SDF-1 expression and help in the improvement of tissue regeneration. Here, we review pivotal roles of HIF-1α /CXCR4/SDF-1 pathway in homing of progenitor/Stem cell which were affected by physical hypoxia as well as various hypoxia-mimicking agents.

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Mingyang Li ◽  
Rong Cong ◽  
Liyu Yang ◽  
Lei Yang ◽  
Yiqi Zhang ◽  
...  

Abstract Bone marrow-derived mesenchymal stem cells (BMSCs) in postmenopausal osteoporosis models exhibit loss of viability and multipotency. Identification of the differentially expressed RNAs in osteoporotic BMSCs could reveal the mechanisms underlying BMSC dysfunction under physiological conditions, which might improve stem cell therapy and tissue regeneration. In this study, we performed high-throughput RNA sequencing and showed that the novel long non-coding RNA (lncRNA) LNC_000052 and its co-expressed mRNA PIK3R1 were upregulated in osteoporotic BMSCs. Knockdown of LNC_000052 could promote BMSC proliferation, migration, osteogenesis, and inhibit apoptosis via the PI3K/Akt signaling pathway. We found that both LNC_000052 and PIK3R1 shared a miRNA target, miR-96-5p, which was downregulated in osteoporotic BMSCs. Their binding sites were confirmed by dual-luciferase assays. Downregulation of miR-96-5p could restrain the effects of LNC_000052 knockdown while upregulation of miR-96-5p together with LNC_000052 knockdown could improve the therapeutic effects of BMSCs. In summary, the LNC_000052–miR-96-5p–PIK3R1 axis led to dysfunction of osteoporotic BMSCs and might be a novel therapeutic target for stem cell therapy and tissue regeneration.


2016 ◽  
Vol 8 (2) ◽  
pp. 61
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya

BACKGROUND: Recent advances in our basic knowledge of the tissue damage and regeneration pathology have combined with a remarkable progress in stem cell biology so the prospect of clinical tissue repair strategies is a tangible reality. We tried to describe a better view about mesenchymal stem cell (MSC) mechanisms in wound healing and tissue regeneration, sending any ideas for next advanced therapies.CONTENT: Sustaining injury, whether minor or major, is part of every organism life. Therefore, efficient response mechanisms to damage have developed. Wound healing is a perplexing multi-step processes which can be divided into three major phases: inflammation, proliferation, and scar formation/remodeling. Though the compartementalization of this process into discrete stages give the illusion of simplicity, but in reality it is much more complicated. So that efficient healing can occur, complex interactions between multiple cell types, soluble factors and extracellular matrix components are required to rebuild the tissue. Even under optimal conditions, the healing process drives to fibrosis or scar. The latest technology that makes a huge difference in the wound healing process is stem cell therapy, which offers a novel approach to many diseases.SUMMARY: Wound healing therapies continue to rapidly evolve, with advances in basic science and engineering research heralding the development of new therapies, as well as ways to modify existing treatments. Stem cell-based therapy is one of the most promising therapeutic concepts for wound healing. Advances in stem cell biology have enabled researchers and clinicians alike with access to cells capable of actively modulating the healing response. KEYWORDS: wound healing, tissue regeneration, stem cells therapy


Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3051-3059 ◽  
Author(s):  
TC Burn ◽  
AB Satterthwaite ◽  
DG Tenen

Abstract The human CD34 hematopoietic stem cell antigen is a highly glycosylated type 1 membrane protein of unknown function. CD34 is expressed on 1% to 4% of bone marrow cells, including pluripotent stem cells and committed progenitors of each hematopoietic lineage. CD34 has also been shown to be expressed on the small vessel endothelium of a variety of tissues and on a subset of bone marrow stromal cells. We have chosen to use the human CD34 gene as model to examine the transcription factors and cis-elements required for stem cell/progenitor cell-specific gene regulation. We show here that the CD34 gene is transcriptionally regulated in tissue culture cells. Using a luciferase reporter gene, we have isolated and characterized an active CD34 promoter. A CD34- luciferase construct, containing 4.5 kb of 5′ flanking DNA from a CD34 genomic clone, was 30-fold more active in CD34+ tissue culture cells than in HeLa cells. Sequences from the 3′ end of the CD34 gene were shown to have enhancing activity in CD34+ T-lymphoblastic RPMI-8402 cells and not in CD34- U937 cells or in nonhematopoietic HeLa cells. We also show that a cytidine-guanosine island in the 5′ end of the CD34 gene is heavily methylated in two CD34- hematopoietic cell lines and demethylated in two CD34+ cell lines. Analysis of the CD34 promoter should result in the identification of stem cell/progenitor cell- specific transcription factors and should provide a means to direct the expression of heterologous genes in hematopoietic stem cells and progenitors.


2019 ◽  
Vol 20 (5) ◽  
pp. 1118 ◽  
Author(s):  
Jordi Camps ◽  
Hanne Grosemans ◽  
Rik Gijsbers ◽  
Christa Maes ◽  
Maurilio Sampaolesi

Progressive muscle degeneration followed by dilated cardiomyopathy is a hallmark of muscular dystrophy. Stem cell therapy is suggested to replace diseased myofibers by healthy myofibers, although so far, we are faced by low efficiencies of migration and engraftment of stem cells. Chemokines are signalling proteins guiding cell migration and have been shown to tightly regulate muscle tissue repair. We sought to determine which chemokines are expressed in dystrophic muscles undergoing tissue remodelling. Therefore, we analysed the expression of chemokines and chemokine receptors in skeletal and cardiac muscles from Sarcoglycan-α null, Sarcoglycan-β null and immunodeficient Sgcβ-null mice. We found that several chemokines are dysregulated in dystrophic muscles. We further show that one of these, platelet-derived growth factor-B, promotes interstitial stem cell migration. This finding provides perspective to an approachable mechanism for improving stem cell homing towards dystrophic muscles.


2007 ◽  
Vol 132 (3) ◽  
pp. 944-954 ◽  
Author(s):  
Philipe N. Khalil ◽  
Véronique Weiler ◽  
Peter J. Nelson ◽  
Maurice N. Khalil ◽  
Sabine Moosmann ◽  
...  

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