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 SDF-1α Gene-Activated Collagen Scaffold Restores Pro-Angiogenic Wound Healing Features in Human Diabetic Adipose-Derived Stem Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 160
Author(s):  
Ashang L. Laiva ◽  
Fergal J. O’Brien ◽  
Michael B. Keogh
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Stem Cell ◽  
Collagen Scaffold ◽  
Diabetic Patients ◽  
Matrix Remodeling ◽  
Adipose Derived Stem Cells ◽  
Cell Therapies ◽  
Gene And Protein Expression ◽  
The Impact

Non-healing diabetic foot ulcers (DFUs) can lead to leg amputation in diabetic patients. Autologous stem cell therapy holds some potential to solve 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). We assessed the impact of the gene-activated scaffold on diabetic ADSCs by comparing their response against healthy ADSCs cultured on a gene-free scaffold over two weeks. Overall, we found that the gene-activated scaffold could restore the 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 gene-activated scaffold induced the overexpression of SDF-1α in diabetic ADSCs and engaged the receptor CXCR7, causing downstream β-arrestin signaling, as effectively as the transfected healthy ADSCs. The transfected diabetic ADSCs also exhibited pro-wound healing features characterized by active matrix remodeling of the provisional fibronectin matrix and basement membrane protein collagen IV. The gene-activated scaffold also induced a controlled pro-healing response in the healthy ADSCs by disabling early developmental factors signaling while promoting the expression of tissue remodeling components. Conclusively, we show that the SDF-1α gene-activated scaffold can overcome the deficiencies associated with diabetic ADSCs, paving the way for autologous stem cell therapies combined with novel biomaterials to treat DFUs.

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.

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.

Stem Cell-Based Therapies: A New Ray of Hope for Diabetic Patients

2019 ◽  
Vol 14 (2) ◽  
pp. 146-151 ◽  
Author(s):  
Junaid Khan ◽  
Amit Alexander ◽  
Mukta Agrawal ◽  
Ajazuddin ◽  
Sunil Kumar Dubey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Drug Therapy ◽  
Type I Diabetes ◽  
Embryonic Stem ◽  
Health Concern ◽  
Future Research ◽  
Diabetic Patients ◽  
Successful Implementation ◽  
Type I

Diabetes and its complications are a significant health concern throughout the globe. There are physiological differences in the mechanism of type-I and type-II diabetes and the conventional drug therapy as well as insulin administration seem to be insufficient to address the problem at large successfully. Hypoglycemic swings, frequent dose adjustments and resistance to the drug are major problems associated with drug therapy. Cellular approaches through stem cell based therapeutic interventions offer a promising solution to the problem. The need for pancreatic transplants in case of Type- I diabetes can also be by-passed/reduced due to the formation of insulin producing β cells via stem cells. Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs), successfully used for generating insulin producing β cells. Although many experiments have shown promising results with stem cells in vitro, their clinical testing still needs more exploration. The review attempts to bring into light the clinical studies favoring the transplantation of stem cells in diabetic patients with an objective of improving insulin secretion and improving degeneration of different tissues in response to diabetes. It also focuses on the problems associated with successful implementation of the technique and possible directions for future research.

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 The Effects of Silver-Releasing Foam Dressings on Diabetic Foot Ulcer Healing

2021 ◽  
Vol 10 (7) ◽  
pp. 1495
Author(s):  
Yu-Chi Wang ◽  
Hsiao-Chen Lee ◽  
Chien-Lin Chen ◽  
Ming-Chun Kuo ◽  
Savitha Ramachandran ◽  
...  
Keyword(s):  
Wound Healing ◽  
Diabetic Foot ◽  
Healing Rate ◽  
Early Period ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Wound Management ◽  
Control Group ◽  
Diabetic Patients ◽  
High Morbidity

Diabetic foot ulcers (DFUs) are a serious complication in diabetic patients and lead to high morbidity and mortality. Numerous dressings have been developed to facilitate wound healing of DFUs. This study investigated the wound healing efficacy of silver-releasing foam dressings versus silver-containing cream in managing outpatients with DFUs. Sixty patients with Wagner Grade 1 to 2 DFUs were recruited. The treatment group received silver-releasing foam dressing (Biatain® Ag Non-Adhesive Foam dressing; Coloplast, Humlebaek, Denmark). The control group received 1% silver sulfadiazine (SSD) cream. The ulcer area in the silver foam group was significantly reduced compared with that in the SSD group after four weeks of treatment (silver foam group: 76.43 ± 7.41%, SSD group: 27.00 ± 4.95%, p < 0.001). The weekly wound healing rate in the silver foam group was superior to the SSD group during the first three weeks of treatment (p < 0.05). The silver-releasing foam dressing is more effective than SSD in promoting wound healing of DFUs. The effect is more pronounced in the initial three weeks of the treatment. Thus, silver-releasing foam could be an effective wound dressing for DFUs, mainly in the early period of wound management.

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