scholarly journals Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc Regeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Kaishun Xia ◽  
Jian Zhu ◽  
Jianming Hua ◽  
Zhe Gong ◽  
Chao Yu ◽  
...  

Background. Cell replacement therapy is an attractive alternative for treating degenerated intervertebral discs (IVDs), which are related to the reduction of nucleus pulposus-like cells (NP-lCs) and the loss of the extracellular matrix. Induced pluripotent stem cells (iPSCs) which resemble embryonic stem cells are considered to be a potential resource for restoring NP-lCs and disc homeostasis. Here, we proposed an efficient two-step differentiation protocol of human iPSCs into NP-lCs and continuously tested their in vivo ability to regenerate IVDs. Methods. A polymeric gelatin microsphere (GM) was generated for sustained release of growth and differentiation factor-5 (GDF-5) and as a cell delivery vehicle of NP-lCs. By injecting NP-lC-seeded GDF-5-loaded GMs into the rat coccygeal intervertebral discs, the disc height and water content were examined with the molybdenum target radiographic imaging test and magnetic resonance imaging examination. Histology and immunohistochemistry results were shown with H&E, S-O-Fast Green, and immunohistochemistry staining. Results. We demonstrated that the injection of NP-lC-seeded GDF-5-loaded GMs could reverse IDD in a rat model. The imaging examination indicated that disc height recovered and water content increased. Histology and immunohistochemistry results indicated that the NP cells as well as their extracellular matrix were partially restored. Conclusions. The results suggest that NP-lC-seeded GDF-5-loaded GMs could partially regenerate degenerated intervertebral discs after transplantation into rat coccygeal intervertebral discs. Our study will help develop a promising method of stem cell-based therapy for IDD.

2018 ◽  
Vol 10 (1) ◽  
pp. 1 ◽  
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya

BACKGROUND: Low back pain (LBP) mostly caused by disc degeneration, reflects to a tremendous of health care system and economy. More knowledge about these underlying pathologies will improve the opportunities that may represent critical therapeutic targets.CONTENT: Basic research is advancing the understanding of the pathogenesis and management of LBP at the molecular and genetic levels. Cytokines such as matrix metalloproteinases, phospholipase A2, nitric oxide, and tumor necrosis factor-α are thought to contribute to the development of LBP. Mesenchymal stem cells (MSCs) transplant to cartilage-like cells and secrete extracellular matrix and encourage nucleus pulposus (NP) cell activity inhibiting NP cell apoptosis, together with some chemical mediators such as cytokines and growth factors become a safe and effective new strategy for intervertebral disc degeneration (IDD) treatment and regeneration.SUMMARY: IDD occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians to help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.KEYWORDS: low back pain (LBP), intervertebral disc (IVD), degeneration, nucleus pulposus (NP), annulus fibrosus (AF), extracellular matrix (ECM), genetic, stem cells


2015 ◽  
Vol 12 (3) ◽  
pp. 4664-4668 ◽  
Author(s):  
KERAN SONG ◽  
TAO GU ◽  
FENG SHUANG ◽  
JIAGUANG TANG ◽  
DONGFENG REN ◽  
...  

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Luqia Hou ◽  
John Coller ◽  
Vanita Natu ◽  
Ngan Huang

Human induced pluripotent stem cell (iPSC)-derived endothelial cells (iPSC-ECs) are a promising cell source for vascular regeneration in patients with peripheral arterial disease. However, a critical bottleneck to their clinical translation is the ability to differentiate the cells reproducibly at high yields. Since endothelial cells interact with the basement membrane extracellular matrix (ECM), we sought to examine the role of ECMs on endothelial differentiation using combinatorial ECM microenvironments. ECM microarrays were developed by covalent conjugation of ECMs (gelatin, fibronectin, laminin, heparin sulfate proteoglycans, collagen IV, matrigel) and the multi-component combinations thereof. The pluripotent stem cells attached to the ECMs and subsequently differentiated over the course of 5 days. Endothelial differentiation was semi-quantitatively scored based on the degree of CD31 staining. Our results demonstrated greater levels of CD31staining when cultured on gelatin + matrigel + laminin (G+M+L) or fibronectin + laminin + heparan sulfate (F+L+H), compared to other combinations across three human pluripotent stem cell lines (iPSC-Huf5, iPSC-CON1, and ESC-H1). This enhancement in endothelial differentiation on the microscale was confirmed at larger cell culture platforms in which a marked increase in CD31+ cells was observed in G+M+L modified-dishes (> 5 fold), and F+L+H combination (> 10 fold), compared to gelatin-modified dishes. RT-PCR further confirmed the transcriptional upregulation in endothelial markers for CD31 (> 2 fold) and VE-cadherin (> 4 fold) on G+M+L, compared to gelatin-modified dishes. To elucidate the role of cell-ECM interactions on endothelial differentiation, gene expression of integrin subunits were examined. Gene expression was markedly upregulated in integrins α1 (>10 fold); α4, α5, and αV (>5 fold); and β1, β3 (>50 fold), and β4, when comparing differentiated cells on day14 to undifferentiated cells. The upregulation of integrin subunits was concomitant with upregulation in endothelial genes. Together, this data suggested that combinatorial ECMs differentially promote endothelial differentiation, in part through integrin-mediated pathways.


Author(s):  
Prithiv K R Kumar

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.


2019 ◽  
Vol 26 (34) ◽  
pp. 6321-6338 ◽  
Author(s):  
Shuaimeng Guan ◽  
Kun Zhang ◽  
Jingan Li

Stem cell transplantation is an advanced medical technology, which brings hope for the treatment of some difficult diseases in the clinic. Attributed to its self-renewal and differential ability, stem cell research has been pushed to the forefront of regenerative medicine and has become a hot topic in tissue engineering. The surrounding extracellular matrix has physical functions and important biological significance in regulating the life activities of cells, which may play crucial roles for in situ inducing specific differentiation of stem cells. In this review, we discuss the stem cells and their engineering application, and highlight the control of the fate of stem cells, we offer our perspectives on the various challenges and opportunities facing the use of the components of extracellular matrix for stem cell attachment, growth, proliferation, migration and differentiation.


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