Ablation of MMP9 induces survival and differentiation of cardiac stem cells into cardiomyocytes in the heart of diabetics: a role of extracellular matrix

2012 ◽  
Vol 90 (3) ◽  
pp. 353-360 ◽  
Author(s):  
Paras Kumar Mishra ◽  
Vishalakshi Chavali ◽  
Naira Metreveli ◽  
Suresh C. Tyagi
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Confocal Microscopy ◽  
Cell Survival ◽  
Troponin I ◽  
Gelatin Zymography ◽  
Cardiac Stem Cells ◽  
Stem Cell Survival

The contribution of extracellular matrix (ECM) to stem cell survival and differentiation is unequivocal, and matrix metalloproteinase-9 (MMP9) induces ECM turn over; however, the role of MMP9 in the survival and differentiation of cardiac stem cells is unclear. We hypothesize that ablation of MMP9 enhances the survival and differentiation of cardiac stem cells into cardiomyocytes in diabetics. To test our hypothesis, Ins2+/− Akita, C57 BL/6J, and double knock out (DKO: Ins2+/−/MMP9−/−) mice were used. We created the DKO mice by deleting the MMP9 gene from Ins2+/−. The above 3 groups of mice were genotyped. The activity and expression of MMP9 in the 3 groups were determined by in-gel gelatin zymography, Western blotting, and confocal microscopy. To determine the role of MMP9 in ECM stiffness (fibrosis), we measured collagen deposition in the histological sections of hearts using Masson’s trichrome staining. The role of MMP9 in cardiac stem cell survival and differentiation was determined by co-immunoprecipitation (co-IP) of MMP9 with c-kit (a marker of stem cells) and measuring the level of troponin I (a marker of cardiomyocytes) by confocal microscopy in the 3 groups. Our results revealed that ablation of MMP9 (i) reduces the stiffness of ECM by decreasing collagen accumulation (fibrosis), and (ii) enhances the survival (elevated c-kit level) and differentiation of cardiac stem cells into cardiomyocytes (increased troponin I) in diabetes. We conclude that inhibition of MMP9 ameliorates stem cell survival and their differentiation into cardiomyocytes in diabetes.

scholarly journals The Emerging Role of PEDF in Stem Cell Biology

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Mina Elahy ◽  
Swati Baindur-Hudson ◽  
Crispin R. Dass
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Biology ◽  
Single Gene ◽  
Stem Cell Biology ◽  
Cell Type ◽  
Stem Cell Survival ◽  
Cell Type Specific

Encoded by a single gene, PEDF is a 50 kDa glycoprotein that is highly conserved and is widely expressed among many tissues. Most secreted PEDF deposits within the extracellular matrix, with cell-type-specific functions. While traditionally PEDF is known as a strong antiangiogenic factor, more recently, as this paper highlights, PEDF has been linked with stem cell biology, and there is now accumulating evidence demonstrating the effects of PEDF in a variety of stem cells, mainly in supporting stem cell survival and maintaining multipotency.

scholarly journals Role of geometrical cues in bone marrow-derived mesenchymal stem cell survival, growth and osteogenic differentiation

2017 ◽  
Vol 32 (7) ◽  
pp. 906-919 ◽  
Author(s):  
Dhanak Gupta ◽  
David M Grant ◽  
Kazi M Zakir Hossain ◽  
Ifty Ahmed ◽  
Virginie Sottile
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Survival ◽  
Osteogenic Differentiation ◽  
Stem Cell Survival

Bone Marrow-Derived Cells Regenerate Kit+ Cardiac Stem Cells (CSCs) in Damaged Heart.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1681-1681
Author(s):  
Francesco Cerisoli ◽  
Lucio Barile ◽  
Roberto Gaetani ◽  
Letizia Cassinelli ◽  
Giacomo Frati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Troponin I ◽  
Regulatory Elements ◽  
Cardiac Cells ◽  
Cardiac Differentiation ◽  
Pcr Analysis ◽  
Cardiac Stem Cells ◽  
Wild Type

Abstract A growing amount of data indicates that the heart harbours stem cells (CSCs) with regenerative potential, however the origin(s) of adult CSCs is still unknown. The expression of Kit a marker of several stem cell types, including hematopoietic and cardiac stem cells, suggests that Kit positive-CSCs may derive, at least in part, from extracardiac sources. In addition, it has been suggested that bone marrow (BM) cells may be mobilized, home into the heart and trans-differentiate into cardiomyocytes, following myocardial infarction. To investigate whether BM cells can contribute to repopulate the cardiac Kit+ stem cell pool, we transplanted BM cells from a mouse line expressing transgenic Green Fluorescent Protein (GFP) under the control of Kit regulatory elements, into wild type irradiated recipients. After hematological reconstution (4–5 months) and following cardiac infarction, cardiac cells were grown in vitro into typical “cardiospheres” (Messina et al., Circ. Res. 95,911;2004). The cardiospheres obtained, although not numerous, were all GFP fluorescent; this result was confirmed by PCR analysis of genomic DNA of individual CSs. At confocal microscopy, cells at the periphery of CSs showed coexistence of low GFP with cardiac markers, such as Troponin I and the transcription factor NKx2.5, consistent with the expected kit downregulation during cardiac differentiation. Our results show that cells of bone marrow origin can give rise, after homing into the heart, to cells with properties of Kit+ CSC. In contrast, CSCs isolated from kit/GFP transgenic mice are not able, upon transplantation, to repopulate the bone marrow of wild-type irradiated recipients. Thus, at least in pathological conditions, part of the Kit-positive CSCs population may be generated by BM-derived cells, capable of adopting in the heart the same function and features of cardiac stem cells.

Investigating The Role Of Nrf2 In Mesenchymal Stem Cell Survival And Function

2012 ◽  
Author(s):  
Umayal Sivagnanalingam ◽  
John Attanasio ◽  
Thomas Mariani ◽  
Patricia J. Sime ◽  
Jody Gascon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Survival ◽  
Stem Cell Survival ◽  
And Function

scholarly journals PTBP1/HNRNP I controls intestinal epithelial cell regeneration by maintaining stem cell survival and stemness

2021 ◽  
Author(s):  
Wesley Tung ◽  
Ullas Valiya Chembazhi ◽  
Jing Yang ◽  
Ka Lam Nguyen ◽  
Aryan Lalwani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Epithelial Cell ◽  
Cell Survival ◽  
Intestinal Epithelial Cell ◽  
Intestinal Stem Cells ◽  
Intestinal Stem Cell ◽  
Cell Regeneration ◽  
Intestinal Epithelial ◽  
Stem Cell Survival

Properly controlled intestinal epithelial cell regeneration is not only vital for protection against insults from environmental hazards but also crucial for preventing intestinal cancer. Intestinal stem cells located in the crypt region provide the driving force for epithelial regeneration, and thus their survival and death must be precisely regulated. We show here that polypyrimidine tract binding protein 1 (PTBP1, also called heterogeneous nuclear ribonucleoprotein I, or HNRNP I), an RNA-binding protein that post-transcriptionally regulates gene expression, is critical for intestinal stem cell survival and stemness. Mechanistically, we show that PTBP1 inhibits the expression of PHLDA3, an AKT repressor, and thereby maintains AKT activity in the intestinal stem cell compartment to promote stem cell survival and proliferation. Furthermore, we show that PTBP1 inhibits the expression of PTBP2, a paralog of PTBP1 that is known to induce neuron differentiation, through repressing inclusion of alternative exon 10 to Ptbp2 transcript. Loss of PTBP1 results in a significant upregulation of PTBP2, which is accompanied by splicing changes in genes that are important for neuron cell development. This finding suggests that PTBP1 prevents aberrant differentiation of intestinal stem cells into neuronal cells through inhibiting PTBP2. Our results thus reveal a novel mechanism whereby PTBP1 maintains intestinal stem cell survival and stemness through the control of gene function post-transcriptionally.

scholarly journals The Role of MicroRNAs in Cardiac Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Nima Purvis ◽  
Andrew Bahn ◽  
Rajesh Katare
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Cardiac Stem Cells ◽  
Cell Therapies ◽  
Small Noncoding Rna ◽  
Proliferation And Differentiation

Stem cells are considered as the next generation drug treatment in patients with cardiovascular disease who are resistant to conventional treatment. Among several stem cells used in the clinical setting, cardiac stem cells (CSCs) which reside in the myocardium and epicardium of the heart have been shown to be an effective option for the source of stem cells. In normal circumstances, CSCs primarily function as a cell store to replace the physiologically depleted cardiovascular cells, while under the diseased condition they have been shown to experimentally regenerate the diseased myocardium. In spite of their major functional role, molecular mechanisms regulating the CSCs proliferation and differentiation are still unknown. MicroRNAs (miRs) are small, noncoding RNA molecules that regulate gene expression at the posttranscriptional level. Recent studies have demonstrated the important role of miRs in regulating stem cell proliferation and differentiation, as well as other physiological and pathological processes related to stem cell function. This review summarises the current understanding of the role of miRs in CSCs. A deeper understanding of the mechanisms by which miRs regulate CSCs may lead to advances in the mode of stem cell therapies for the treatment of cardiovascular diseases.

scholarly journals Evaluation of human dental stem cell growth characteristics and cellular morphological changes in response to extracellular matrix nanotopography

2019 ◽  
Author(s):  
Vaishnavi Dhanvantri ◽  
R Ramya ◽  
Kotturathu Mammen Cherian ◽  
Balasundari Ramesh
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Survival ◽  
Morphological Changes ◽  
Growth Characteristics ◽  
Conditioned Media ◽  
Differentiation Potential ◽  
Soluble Factors ◽  
Stem Cell Survival ◽  
Dental Stem Cell

Objective: Nanotopography and soluble extracellular factors are present in the dental stem cell niche in the pulp. Their effect on dental stem cell survival and differentiation is yet to be established. We aimed to analyze the individual and combined roles of extracellular matrix (ECM) nanotopography and serum (soluble factors) on the growth, differentiation potential, and morphological characteristics of the human dental pulp stem cells (hDPSC). This study aimed to evaluate and compare the hDPSC response to different environmental cues – nanofibers, serum, and conditioned media. Materials and methods: In this study, fabricated PLLA nanofibers were used as the in vitro structural biomimetic of the native nanotopography found in the in vivo ECM/stem cell niche. Serum and conditioned media were used as the in vitro mimic of the soluble factors to which stem cells get exposed in vivo. hDPSC were grown in the presence and absence of biodegradablepoly-L-lactic-acid nanofibers and serum. The growth characteristics of hDPSC were assessed in terms of cell viability and doubling time at the interval of every passage. Cellular morphological changes were studied using inverted microscopy and H&E. As the second part of the study, hDPSC in all culture conditions were exposed to Dental Pulp Conditioned Media (DPCM) for a short duration of 3 days. After transient exposure to DPCM, the growth characteristics and the morphological changes of hDPSC were assessed. In addition, scanning electron microscopy was used for the morphological study of hDPSC on nanofibers, exposed to conditioned media. The differentiated cells were analyzed by qRT-PCR for neurogenic and odontogenic expression of RUNX2, osteopontin, and β-tubulin III genes. Results: hDPSC showed better survival and proliferation in the presence of nanofibers and serum. Absence of nanofibers or serum greatly altered stem cell survival and proliferation and also indicated differentiation. In addition, it was observed that after transient exposure to DPCM, the presence of both PLLA nanofiber and serum favoured higher odontogenic and neurogenic differentiation potential, without characteristic morphological changes of terminal differentiation. Conclusion: hDPSC has the ability to sense nanoscale geometric cues from their microenvironment. Nanotopography and soluble factors of the extracellular matrix both affect hDPSC. Further studies are essential to identify the key pathways that play a vital role in such interactions. The hDPSC demonstrated better survival and proliferation in the presence of nanofibers and serum. Absence of nanofibers or serum greatly altered stem cell survival and proliferation and also showed changes indicative of differentiation. The results were compared and analyzed using GraphPad Prism 5 Software. hDPSC possess the ability to sense nanoscale geometric cues from their microenvironment. Nanotopography and soluble factors of the Extracellular matrix together influence the fate of hDPSC. Further studies are essential to identify the key pathways that play a vital role in such interactions.

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