scholarly journals Adipose-Derived Stem Cells Secretome and Its Potential Application in “Stem Cell-Free Therapy”

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 878
Author(s):  
Anna Trzyna ◽  
Agnieszka Banaś-Ząbczyk
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Stem Cell ◽  
Growth Factors ◽  
Treatment Strategies ◽  
Adipose Derived Stem Cells ◽  
Cell Based Therapy ◽  
Current State ◽  
Non Coding Rnas ◽  
New Treatment

Adipose-derived stem cells (ASCs) secrete many cytokines, proteins, growth factors, and extracellular vesicles with beneficial outcomes that can be used in regenerative medicine. It has great potential, and the development of new treatment strategies using the ASCs secretome is of global interest. Besides cytokines, proteins, and growth factors, the therapeutic effect of secretome is hidden in non-coding RNAs such as miR-21, miR-24, and miR-26 carried via exosomes secreted by adequate cells. The whole secretome, including ASC-derived exosomes (ASC-exos) has been proven in many studies to have immunomodulatory, proangiogenic, neurotrophic, and epithelization activity and can potentially be used for neurodegenerative, cardiovascular, respiratory, inflammatory, and autoimmune diseases as well as wound healing treatment. Due to limitations in the use of stem cells in cell-based therapy, its secretome with emphasis on exosomes seems to be a reasonable and safer alternative with increased effectiveness and fewer side effects. Moreover, the great advantage of cell-free therapy is the possibility of biobanking the ASCs secretome. In this review, we focus on the current state of knowledge on the use of the ASCs secretome in stem cell-free therapy.

Application of Nanomaterials in Regulating the Fate of Adipose-derived Stem Cells

2021 ◽  
Vol 16 (1) ◽  
pp. 3-13
Author(s):  
Lang Wang ◽  
Yong Li ◽  
Maorui Zhang ◽  
Kui Huang ◽  
Shuanglin Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Research ◽  
Adult Stem Cells ◽  
Adipose Derived Stem Cells ◽  
Proliferation And Differentiation ◽  
Recent Developments ◽  
Good Biocompatibility ◽  
Regulatory Effects ◽  
New Treatment

Adipose-derived stem cells are adult stem cells which are easy to obtain and multi-potent. Stem-cell therapy has become a promising new treatment for many diseases, and plays an increasingly important role in the field of tissue repair, regeneration and reconstruction. The physicochemical properties of the extracellular microenvironment contribute to the regulation of the fate of stem cells. Nanomaterials have stable particle size, large specific surface area and good biocompatibility, which has led them being recognized as having broad application prospects in the field of biomedicine. In this paper, we review recent developments of nanomaterials in adipose-derived stem cell research. Taken together, the current literature indicates that nanomaterials can regulate the proliferation and differentiation of adipose-derived stem cells. However, the properties and regulatory effects of nanomaterials can vary widely depending on their composition. This review aims to provide a comprehensive guide for future stem-cell research on the use of nanomaterials.

scholarly journals “Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Cardiac Cells ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Micro Rnas ◽  
New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

scholarly journals Anti-Aging β-Klotho Gene-Activated Scaffold Promotes Rejuvenative Wound Healing Response in Human Adipose-Derived Stem Cells

2021 ◽  
Vol 14 (11) ◽  
pp. 1168
Author(s):  
Ashang L. Laiva ◽  
Fergal J. O’Brien ◽  
Michael B. Keogh
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Basement Membrane ◽  
Collagen Iv ◽  
Dermal Fibroblasts ◽  
Adipose Derived Stem Cells ◽  
Ki 67 ◽  
Matrix Deposition ◽  
Klotho Gene ◽  
Cell Based Therapy

Wound healing requires a tight orchestration of complex cellular events. Disruption in the cell-signaling events can severely impair healing. The application of biomaterial scaffolds has shown healing potential; however, the potential is insufficient for optimal wound maturation. This study explored the functional impact of a collagen-chondroitin sulfate scaffold functionalized with nanoparticles carrying an anti-aging gene β-Klotho on human adipose-derived stem cells (ADSCs) for rejuvenative healing applications. We studied the response in the ADSCs in three phases: (1) transcriptional activities of pluripotency factors (Oct-4, Nanog and Sox-2), proliferation marker (Ki-67), wound healing regulators (TGF-β3 and TGF-β1); (2) paracrine bioactivity of the secretome generated by the ADSCs; and (3) regeneration of basement membrane (fibronectin, laminin, and collagen IV proteins) and expression of scar-associated proteins (α-SMA and elastin proteins) towards maturation. Overall, we found that the β-Klotho gene-activated scaffold offers controlled activation of ADSCs’ regenerative abilities. On day 3, the ADSCs on the gene-activated scaffold showed enhanced (2.5-fold) activation of transcription factor Oct-4 that was regulated transiently. This response was accompanied by a 3.6-fold increase in the expression of the anti-fibrotic gene TGF-β3. Through paracrine signaling, the ADSCs-laden gene-activated scaffold also controlled human endothelial angiogenesis and pro-fibrotic response in dermal fibroblasts. Towards maturation, the ADSCs-laden gene-activated scaffold further showed an enhanced regeneration of the basement membrane through increases in laminin (2.1-fold) and collagen IV (8.8-fold) deposition. The ADSCs also expressed 2-fold lower amounts of the scar-associated α-SMA protein with improved qualitative elastin matrix deposition. Collectively, we determined that the β-Klotho gene-activated scaffold possesses tremendous potential for wound healing and could advance stem cell-based therapy for rejuvenative healing applications.

scholarly journals The Beneficial Potential of Genetically Modified Stem Cells in the Treatment of Stroke: A Review

2020 ◽  
Author(s):  
Mohammad Saied Salehi ◽  
Anahid Safari ◽  
Sareh Pandamooz ◽  
Benjamin Jurek ◽  
Etrat Hooshmandi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Current Knowledge ◽  
Infarct Volume ◽  
Genetically Modified ◽  
Functional Improvement ◽  
Differentiation Potential ◽  
Therapeutic Efficiency ◽  
Cell Based Therapy

The last two decades have witnessed a surge in investigations proposing stem cells as a promising strategy to treat stroke. Since growth factor release is considered as one of the most important aspects of cell-based therapy, stem cells over-expressing growth factors are hypothesized to yield higher levels of therapeutic efficiency. In pre-clinical studies of the last 15 years that were investigating the efficiency of stem cell therapy for stroke, a variety of stem cell types were genetically modified to over-express various factors. In this review we summarize the current knowledge on the therapeutic efficiency of stem cell-derived growth factors, encompassing techniques employed and time points to evaluate. In addition, we discuss several types of stem cells, including the recently developed model of epidermal neural crest stem cells, and genetically modified stem cells over-expressing specific factors, which could elevate the restorative potential of naive stem cells. The restorative potential is based on enhanced survival/differentiation potential of transplanted cells, apoptosis inhibition, infarct volume reduction, neovascularization or functional improvement. Since the majority of studies have focused on the short-term curative effects of genetically engineered stem cells, we emphasize the need to address their long-term impact.

scholarly journals Adipose-derived stem cells for tissue engineering and therapy of non-healing wounds

2018 ◽  
Vol 72 ◽  
pp. 806-821 ◽  
Author(s):  
Adriana Schumacher ◽  
Mirosława Cichorek ◽  
Michał Pikuła
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Wound Healing ◽  
Clinical Trials ◽  
Adipose Tissue ◽  
Growth Factors ◽  
Chronic Wounds ◽  
Clinical Effects ◽  
Adipose Derived Stem Cells ◽  
Healing Wounds

Chronic wounds seem to be a big problem for the medicinal, social and commercial area, especially for elder patients or people with cancer, metabolic or autoimmune diseases. In this respect, in the modern regenerative medicine there are intensive studies on methodologies that stimulate healing of chronic wounds (diabetic foots, ulcers, burns). In tissue engineering new solutions in wound healing are based on cellular therapies which consisting of growth factors and various types of scaffolds. In this way, there are created skin substitutes which are composed of cellular auto/allografts (stem cells and differentiated cells) and most commonly biodegradable scaffolds; they aim is not only to fill the tissue but also to stimulate wound healing. In this article we demonstrate the current knowledge about biological properties of Adipose- -derived Stem Cells (ASCs), methods of their isolation and potential for use in therapies for non-healing wounds. Adipose tissue seems to be an attractive and abundant stem cells source with therapeutic applicability in diverse phase of the repair and regeneration of the chronically damaged tissues. Additionally, it is believed that secreted by ASCs growth factors, cytokines and exosomes are decisive in the clinical effects. In this review, we also present the current clinical trials using stem cells derived from adipose tissue. Increasingly, the use of cell therapy in wound healing treatment draws attention to the safety, reproducibility and quality of stem cells. Researches go on and therapy approaches are possible but the detailed knowledge of the ASCs biology must be thoroughly investigated before these cells would be widely used in the clinical trials.

scholarly journals An SDF-1α gene-activated collagen scaffold restores pro-angiogenic wound healing features in human diabetic adipose-derived stem cells

2020 ◽  
Author(s):  
Ashang Luwang Laiva ◽  
Fergal J. O’Brien ◽  
Michael B. Keogh
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Stem Cell ◽  
Diabetic Foot ◽  
Diabetic Patients ◽  
Matrix Remodeling ◽  
Adipose Derived Stem Cells ◽  
Matrix Deposition ◽  
Freeze Dried ◽  
Gene And Protein Expression

Abstract Background Diabetic foot ulcer is one of the leading causes of leg amputation and mortality in diabetic patients. Autologous stem cell therapy holds some potential to be a solution to this problem, however diabetic stem cells are relatively dysfunctional and restrictive in their wound healing abilities. This study sought to explore if a novel collagen-chondroitin sulfate (coll-CS) scaffold functionalized with polyplex nanoparticles carrying the gene encoding for stromal-derived factor-1 alpha (SDF-1α gene-activated scaffold) can enhance the regenerative functionality of human diabetic adipose-derived stem cells (ADSCs). Methods Gene-activated scaffolds were first prepared by soak-loading polyethyleneimine nanoparticles carrying the plasmid encoding for SDF-1α gene into a freeze-dried coll-CS scaffold. ADSCs from healthy and diabetic donors were then seeded on the gene-activated scaffold. The response of the ADSCs in the gene-activated scaffold was then compared against those of the healthy ADSCs cultured on the gene-free scaffold over 2 weeks period. Functional response in the ADSCs such as the activation of SDF-1α mediated signaling, production of bioactive factors, pro-angiogenic bioactivity of secreted factors, matrix deposition and remodeling was determined using proteome profiling, Matrigel assay, qRT-PCR and immunofluorescence. Results Overall, we found that SDF-1α gene-activated scaffold could restore pro-angiogenic regenerative response in the human diabetic ADSCs similar to the healthy ADSCs on the gene-free scaffold. Gene and protein expression analysis revealed that the SDF-1α gene-activated scaffold induced the overexpression of SDF-1α in diabetic ADSCs and engaged the receptor CXCR7, causing downstream signaling of β-arrestin as effectively as the transfected healthy ADSCs. The transfected diabetic ADSCs also effectively stimulated angiogenesis in endothelial cells while undergoing matrix remodeling characterized by reduction in deposition of fibronectin matrix and increase in the expression of basement membrane protein collagen IV. The SDF-1α gene-activated scaffold also induced a controlled pro- healing response in the healthy ADSCs by disabling the signaling of early developmental factors while promoting the expression of tissue remodeling components. Conclusion We show that the SDF-1α gene-activated scaffold can overcome the deficiencies associated with diabetic ADSCs paving the way for autologous patient stem cell therapies in combination with novel biomaterials to treat diabetic foot ulcers.

scholarly journals An SDF-1α Gene-activated Collagen Scaffold Restores Pro-angiogenic Wound Healing Features in Human Diabetic Adipose-derived Stem Cells

2020 ◽  
Author(s):  
Ashang Luwang Laiva ◽  
Fergal J. O’Brien ◽  
Michael B. Keogh
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Stem Cell ◽  
Diabetic Foot ◽  
Diabetic Patients ◽  
Matrix Remodeling ◽  
Adipose Derived Stem Cells ◽  
Matrix Deposition ◽  
Freeze Dried ◽  
Gene And Protein Expression

Abstract Background: Diabetic foot ulcer is one of the leading causes of leg amputation and mortality in diabetic patients. Autologous stem cell therapy holds some potential to be a solution to this problem, however diabetic stem cells are relatively dysfunctional and restrictive in their wound healing abilities. This study sought to explore if a novel collagen-chondroitin sulfate (coll-CS) scaffold functionalized with polyplex nanoparticles carrying the gene encoding for stromal-derived factor-1 alpha (SDF-1α gene-activated scaffold) can enhance the regenerative functionality of human diabetic adipose-derived stem cells (ADSCs). Methods: Gene-activated scaffolds were first prepared by soak-loading polyethyleneimine nanoparticles carrying the plasmid encoding for SDF-1α gene into a freeze-dried coll-CS scaffold. ADSCs from healthy and diabetic donors were then seeded on the gene-activated scaffold. The response of the ADSCs in the gene-activated scaffold was then compared against those of the healthy ADSCs cultured on the gene-free scaffold over 2 weeks period. Functional response in the ADSCs such as the activation of SDF-1α mediated signaling, production of bioactive factors, pro-angiogenic bioactivity of secreted factors, matrix deposition and remodeling was determined using proteome profiling, Matrigel assay, qRT-PCR and immunofluorescence.Results: Overall, we found that SDF-1α gene-activated scaffold could restore pro-angiogenic regenerative response in the human diabetic ADSCs similar to the healthy ADSCs on the gene-free scaffold. Gene and protein expression analysis revealed that the SDF-1α gene-activated scaffold induced the overexpression of SDF-1α in diabetic ADSCs and engaged the receptor CXCR7, causing downstream signaling of β-arrestin as effectively as the transfected healthy ADSCs. The transfected diabetic ADSCs also effectively stimulated angiogenesis in endothelial cells while undergoing matrix remodeling characterized by reduction in deposition of fibronectin matrix and increase in the expression of basement membrane protein collagen IV. The SDF-1α gene-activated scaffold also induced a controlled pro- healing response in the healthy ADSCs by disabling the signaling of early developmental factors while promoting the expression of tissue remodeling components.Conclusion: We show that the SDF-1α gene-activated scaffold can overcome the deficiencies associated with diabetic ADSCs paving the way for autologous patient stem cell therapies in combination with novel biomaterials to treat diabetic foot ulcers.

scholarly journals A mathematical model of cartilage regeneration after chondrocyte and stem cell implantation – I: the effects of growth factors

2019 ◽  
Vol 10 ◽  
pp. 204173141982779
Author(s):  
Kelly Campbell ◽  
Shailesh Naire ◽  
Jan Herman Kuiper
Keyword(s):  
Mathematical Model ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Healing Process ◽  
Experimental Studies ◽  
Cartilage Regeneration ◽  
Long Term Results ◽  
Cell Based Therapy

Autologous chondrocyte implantation is a cell-based therapy for treating chondral defects. The procedure begins by inserting chondrocytes into the defect region. The chondrocytes initiate healing by proliferating and depositing extracellular matrix, which allows them to migrate into the defect until it is completely filled with new cartilage. Mesenchymal stem cells can be used instead of chondrocytes with similar long-term results. The main differences are at early times since mesenchymal stem cells must first differentiate into chondrocytes before cartilage is formed. To better understand this repair process, we present a mathematical model of cartilage regeneration after cell therapy. We extend our previous work to include the cell–cell interaction between mesenchymal stem cells and chondrocytes via growth factors. Our results show that matrix formation is enhanced at early times in the presence of growth factors. This study reinforces the importance of mesenchymal stem cell and chondrocyte interaction in the cartilage healing process as hypothesised in experimental studies.

scholarly journals The Effect of Adipose-Derived Stem Cells on Wound Healing: Comparison of Methods of Application

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Hyeonwoo Kim ◽  
Mi Ri Hyun ◽  
Sang Wha Kim
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Imaging System ◽  
Medical Problem ◽  
Adipose Derived Stem Cells ◽  
Control Groups ◽  
Impaired Wound Healing ◽  
Wound Area ◽  
Cell Based Therapy ◽  
Thickness Skin

Impaired wound healing is a significant medical problem. Recently, cell-based therapy focused on stem cells has been developed to overcome the challenges of defective wound healing. In this study, we aimed to evaluate the effectiveness of adipose-derived stem cells (ASCs) in promoting wound healing, using different techniques for administering them. Dorsal full-thickness skin defects (1×1 cm) were created in three groups of mice that received intravenous ASCs by intravenous injection, intramuscular injection, and topical application, respectively. Three control groups received saline in the same ways. Wound healing was assessed clinically, wounds were examined histologically, and GFP-labelled ASCs were detected with an IVIS imaging system. The results revealed that ASCs accelerated wound healing independent of their mode of administration. Histological examination showed that the ASCs accelerated reepithelialization, and IVIS analysis indicated that many ASCs were present in the wound area and disappeared after wound healing.

scholarly journals Prospects of Therapeutic Target and Directions for Ischemic Stroke

2021 ◽  
Vol 14 (4) ◽  
pp. 321
Author(s):  
Jung Hak Kim ◽  
So Young Kim ◽  
Bokyung Kim ◽  
Sang Rae Lee ◽  
Sang Hoon Cha ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Imaging Techniques ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Neurological Deficits ◽  
Cell Based Therapy

Stroke is a serious, adverse neurological event and the third leading cause of death and disability worldwide. Most strokes are caused by a block in cerebral blood flow, resulting in neurological deficits through the death of brain tissue. Recombinant tissue plasminogen activator (rt-PA) is currently the only immediate treatment medication for stroke. The goal of rt-PA administration is to reduce the thrombus and/or embolism via thrombolysis; however, the administration of rt-PA must occur within a very short therapeutic timeframe (3 h to 6 h) after symptom onset. Components of the pathological mechanisms involved in ischemic stroke can be used as potential biomarkers in current treatment. However, none are currently under investigation in clinical trials; thus, further studies investigating biomarkers are needed. After ischemic stroke, microglial cells can be activated and release inflammatory cytokines. These cytokines lead to severe neurotoxicity via the overactivation of microglia in prolonged and lasting insults such as stroke. Thus, the balanced regulation of microglial activation may be necessary for therapy. Stem cell therapy is a promising clinical treatment strategy for ischemic stroke. Stem cells can increase the functional recovery of damaged tissue after post-ischemic stroke through various mechanisms including the secretion of neurotrophic factors, immunomodulation, the stimulation of endogenous neurogenesis, and neovascularization. To investigate the use of stem cell therapy for neurological diseases in preclinical studies, however, it is important to develop imaging technologies that are able to evaluate disease progression and to “chase” (i.e., track or monitor) transplanted stem cells in recipients. Imaging technology development is rapidly advancing, and more sensitive techniques, such as the invasive and non-invasive multimodal techniques, are under development. Here, we summarize the potential risk factors and biomarker treatment strategies, stem cell-based therapy and emerging multimodal imaging techniques in the context of stroke. This current review provides a conceptual framework for considering the therapeutic targets and directions for the treatment of brain dysfunctions, with a particular focus on ischemic stroke.

Sign in / Sign up

Export Citation Format

Share Document