Extracellular Matrix Scaffolds - A Tissue-Specific Bioactive Niche for Stem Cells in Regenerative Therapy

Aiming to restore the normal function of diseased or injured tissues, regenerative therapy approaches are generally based on the engineering of complex tissue-mimicking grafts, encompassing biomaterial scaffolds, stem cells, or their combinations [1-4]. Due to the major role of stem cells in physiological regenerative mechanisms, regenerative therapies normally rely on either stem cells transplantation or stem cell recruitment from the neighboring tissue into the implanted scaffold

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Regrow or Repair: An Update on Potential Regenerative Therapies for the Kidney

Journal of the American Society of Nephrology ◽

10.1681/asn.2021081073 ◽

2021 ◽

pp. ASN.2021081073

Author(s):

Melissa Little ◽

Benjamin Humphreys

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Kidney Development ◽

Transcriptional Analysis ◽

Cell Recruitment ◽

Renal Stem Cells ◽

Induced Pluripotent ◽

Stem Cell Populations ◽

A Site ◽

Regenerative Therapies

Fifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.

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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y11-131 ◽

2012 ◽

Vol 90 (3) ◽

pp. 353-360 ◽

Cited By ~ 31

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.

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The effect of age on stem cell function and utility for therapy

Cell Medicine ◽

10.1177/2155179018773756 ◽

2018 ◽

Vol 10 ◽

pp. 215517901877375 ◽

Cited By ~ 5

Author(s):

Patrick Narbonne

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Function ◽

Regenerative Therapy ◽

Aged Patient ◽

Extrinsic Factors ◽

Aged Patients ◽

Differentiated Cells ◽

Regenerative Therapies ◽

Effect Of Age

During development, stem cells generate all of the differentiated cells that populate our tissues and organs. Stem cells are also responsible for tissue turnover and repair in adults, and as such, they hold tremendous promise for regenerative therapy. Aging, however, impairs the function of stem cells and is thus a significant roadblock to using stem cells for therapy. Paradoxically, the patients who would benefit the most from regenerative therapies are usually advanced in age. The use of stem cells from young donors or the rejuvenation of aged patient-derived stem cells may represent part of a solution. Nonetheless, the transplantation success of young or rejuvenated stem cells in aged patients is still problematic, since stem cell function is greatly influenced by extrinsic factors that become unsupportive with age. This article briefly reviews how aging impairs stem cell function, and how this has an impact on the use of stem cells for therapy.

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Regenerative Therapies in Neonatology: Clinical Perspectives

Klinische Pädiatrie ◽

10.1055/s-0032-1316296 ◽

2012 ◽

Vol 224 (04) ◽

pp. 233-240 ◽

Cited By ~ 8

Author(s):

L. Gortner ◽

U. Felderhoff-Müser ◽

D. Monz ◽

K. Bieback ◽

H. Klüter ◽

...

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Stem Cell ◽

Regenerative Therapy ◽

Controlled Clinical Trials ◽

Term Neonates ◽

Promising Tool ◽

High Risk Infants ◽

Regenerative Therapies ◽

Ischemic Encephalopathy

AbstractRegenerative therapy based on stem cells is applied as standard therapy in pediatric oncology. Furthermore, they are frequently used to treat immunodeficiency disorders of infants. For severe neonatal diseases, e. g. hypoxic-ischemic encephalopathy in term neonates or bronchopulmonary dysplasia in preterm infants, animal models have been established. According to some first preclinical results stem cell administration appears as a promising tool to improve the clinical outcome in high-risk infants. Provided the benefit of regenerative therapies can further be evaluated in appropriate preclinical neonate models, carefully controlled clinical trials to assess the significance of regenerative therapies, such as autologous stem cell administration, are indicated.

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Features of Microsystems for Cultivation and Characterization of Stem Cells with the Aim of Regenerative Therapy

Stem Cells International ◽

10.1155/2016/6023132 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Kihoon Ahn ◽

Sung-Hwan Kim ◽

Gi-Hun Lee ◽

SeungJin Lee ◽

Yun Seok Heo ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Microfluidic Channel ◽

Cell Types ◽

Regenerative Therapy ◽

Human Disorders ◽

Regenerative Therapies ◽

Physical Principles

Stem cells have infinite potential for regenerative therapy thanks to their advantageous ability which is differentiable to requisite cell types for recovery and self-renewal. The microsystem has been proved to be more helpful to stem cell studies compared to the traditional methods, relying on its advantageous feature of mimickingin vivocellular environments as well as other profitable features such as minimum sample consumption for analysis and multiprocedures. A wide variety of microsystems were developed for stem cell studies; however, regenerative therapy-targeted applications of microtechnology should be more emphasized and gain more attractions since the regenerative therapy is one of ultimate goals of biologists and bioengineers. In this review, we introduce stem cell researches harnessing well-known microtechniques (microwell, micropattern, and microfluidic channel) in view point of physical principles and how these systems and principles have been implemented appropriately for characterizing stem cells and finding possible regenerative therapies. Biologists may gain information on the principles of microsystems to apply them to find solutions for their current challenges, and engineers may understand limitations of the conventional microsystems and find new chances for further developing practical microsystems. Through the well combination of engineers and biologists, the regenerative therapy-targeted stem cell researches harnessing microtechnology will find better suitable treatments for human disorders.

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Abstract 498: Combinatorial Extracellular Matrix Microarrays for Probing Endothelial Differentiation of Human Induced Pluripotent Stem Cells

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.498 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Luqia Hou ◽

John Coller ◽

Vanita Natu ◽

Ngan Huang

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Extracellular Matrix ◽

Endothelial Cells ◽

Stem Cell ◽

Pluripotent Stem Cells ◽

Pluripotent Stem Cell ◽

Endothelial Differentiation ◽

Induced Pluripotent

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.

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The Emerging Role of PEDF in Stem Cell Biology

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/239091 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 9

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.

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Recent Advances in Extracellular Matrix for Engineering Stem Cell Responses

Current Medicinal Chemistry ◽

10.2174/0929867326666190704121309 ◽

2019 ◽

Vol 26 (34) ◽

pp. 6321-6338 ◽

Cited By ~ 2

Author(s):

Shuaimeng Guan ◽

Kun Zhang ◽

Jingan Li

Keyword(s):

Stem Cells ◽

Extracellular Matrix ◽

Stem Cell ◽

Cell Attachment ◽

Biological Significance ◽

Engineering Application ◽

Advanced Medical Technology ◽

Challenges And Opportunities ◽

Physical Functions ◽

Differential Ability

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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Stem Cells in the Path of Light, from Corneal to Retinal Reconstruction

Biomedicines ◽

10.3390/biomedicines9080873 ◽

2021 ◽

Vol 9 (8) ◽

pp. 873

Author(s):

Ovidiu Samoila ◽

Lacramioara Samoila

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Clinical Success ◽

Corneal Stroma ◽

Cell Transplant ◽

Inclusion Criteria ◽

Epithelial Stem Cells ◽

Corneal Epithelial ◽

Stem Cells Transplantation ◽

Limbal Epithelial Stem Cells

The future of eye reconstruction invariably includes stem cells transplantation. Corneal limbus, corneal stroma, trabeculum, retinal cells, optic nerve, and all structures that are irreversibly damaged and have no means to be repaired or replaced, through conventional treatment or surgery, represent targets for stem cell reconstruction. This review tries to answer the question if there is any clinical validation for stem therapies, so far, starting from the cornea and, on the path of light, arriving to the retina. The investigation covers the last 10 years of publications. From 2385 published sources, we found 56 clinical studies matching inclusion criteria, 39 involving cornea, and 17 involving retina. So far, corneal epithelial reconstruction seems well validated clinically. Enough clinical data are collected to allow some form of standardization for the stem cell transplant procedures. Cultivated limbal epithelial stem cells (CLET), simple limbal epithelial transplant (SLET), and oral mucosa transplantation are implemented worldwide. In comparison, far less patients are investigated in retinal stem reconstructions, with lower anatomical and clinical success, so far. Intravitreal, subretinal, and suprachoroidal approach for retinal stem therapies face specific challenges.

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