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 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 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 The Effect of Age on the Regenerative Potential of Human Eyelid Adipose-Derived Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Mingqi Zhang ◽  
Zhuoshi Wang ◽  
Yan Zhao ◽  
Lirong Zhang ◽  
Ling Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Adipogenic Differentiation ◽  
Culture Method ◽  
Explant Culture ◽  
Adipose Derived Stem Cells ◽  
Cell Therapies ◽  
Age Related ◽  
Autologous Mesenchymal Stem Cells

Human eyelid adipose-derived stem cells (HEASCs) are a new source of autologous mesenchymal stem cells, which are derived from neuroectoderm and potentially applied in the tissue regeneration and cell therapies. Based on the prevalence of blepharoplasty in Asia and the availability of HEASCs, we investigated the effect of donor age on their characteristics and regenerative potential of HEASCs in vitro. The HEASCs were isolated from patients of three groups: (1) <20 years (n=4), (2) >20 years, <45 years (n=5), and (3) >55 years (n=4). For each group, the proliferative capacity, colony-forming ability, surface markers, differentiation ability, wound healing function, and secreted protein were contrastively evaluated and quantified for statistical analysis. It was found that HEASCs were successfully isolated and cultured by an explant culture method. The proliferative rates, osteogenic and chondrogenic differentiation potentials, wound healing ability, and the expression of TGF-β1 and fibronectin protein of HEASCs significantly decreased as age increased. However, the expression of CD90 antigen and the adipogenic differentiation showed an age-related increase in HEASCs. As many degenerative diseases increase in prevalence with age, the age-related changes of the HEASCs proliferation potential, differentiation capacity, and wound healing ability should be taken into account whenever they are intended for use in research or cytotherapy.

Effect of Collagen Scaffold With Bcl-2-Modified Adipose-Derived Stem Cells on Diabetic Mice Wound Healing

2019 ◽  
Vol 19 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Sheng Ding ◽  
Ye Xu ◽  
Xin Yan ◽  
Yue Lin ◽  
Qian Tan
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Collagen Scaffold ◽  
Control Group ◽  
Skin Defect ◽  
Adipose Derived Stem Cells ◽  
Diabetic Mice ◽  
Group D ◽  
Hematoxylin Eosin ◽  
Scaffold Group

This study aimed at evaluating the effects of collagen scaffold with Bcl-2-modified adipose-derived stem cells (ADSCs) on wound repair in streptozotocin-induced diabetic mice. A round full thickness skin defect with a diameter of 7 mm was made in the mice model. The experimental mice were divided into 4 groups (n = 12 each): group A (control group), group B (scaffold group), group C (ADSCs-scaffold group), and group D (Bcl-2-ADSCs-scaffold group). On days 3, 7, 10, and 14 after surgery, characteristics of wound healing was observed, and wound tissues were sampled for histology characteristics via hematoxylin-eosin staining and immunohistochemical staining. Compared with other groups, the wound healing rate was significantly higher in group D a week after operation ( P < .05). On the seventh day postoperation, group D exhibited higher blood vessel in the wounds granulation tissue than other groups according to results of hematoxylin-eosin staining and immunohistochemistry. In conclusion, these findings demonstrated that collagen scaffold with Bcl-2 modified ADSCs may effectively improve the wound healing process in diabetic mice.

scholarly journals Effect of Pig-Adipose-Derived Stem Cells’ Conditioned Media on Skin Wound-Healing Characteristics In Vitro

2021 ◽  
Vol 22 (11) ◽  
pp. 5469
Author(s):  
Joanna Wiśniewska ◽  
Magda Słyszewska ◽  
Karolina Stałanowska ◽  
Katarzyna Walendzik ◽  
Marta Kopcewicz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Three Dimensional ◽  
Dermal Fibroblasts ◽  
Conditioned Media ◽  
Adipose Derived Stem Cells ◽  
Skin Wound Healing ◽  
Cell Functions ◽  
The Impact

The primary mechanism by which adipose-derived stem cells (ASCs) exert their reparative or regenerative potential relies predominantly on paracrine action. Secretory abilities of ASCs have been found to be amplified by hypoxia pre-conditioning. This study investigates the impact of hypoxia (1% O2) on the secretome composition of pig ASCs (pASCs) and explores the effect of pASCs’ conditioned media (CM) on skin cell functions in vitro and the expression of markers attributed to wound healing. Exposure of pASCs to hypoxia increased levels of vascular endothelial growth factor (VEGF) in CM-Hyp compared to CM collected from the cells cultured in normoxia (CM-Nor). CM-Hyp promoted the migratory ability of pig keratinocytes (pKERs) and delayed migration of pig dermal fibroblasts (pDFs). Exposure of pKERs to either CM-Nor or CM-Hyp decreased the levels of pro-fibrotic indicators WNT10A and WNT11. Furthermore, CM-Hyp enhanced the expression of KRT14, the marker of the basal epidermis layer. In contrast, CM-Nor showed a stronger effect on pDFs manifested by increases in TGFB1, COL1A1, COL3A1, and FN1 mRNA expression. The formation of three-dimensional endothelial cell networks was improved in the presence of CM-Hyp. Overall, our results demonstrate that the paracrine activity of pASCs affects skin cells, and this property might be used to modulate wound healing.

scholarly journals Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson’s Disease

2018 ◽  
Vol 27 (3) ◽  
pp. 456-470 ◽  
Author(s):  
Kang Chi ◽  
Ru-Huei Fu ◽  
Yu-Chuen Huang ◽  
Shih-Yin Chen ◽  
Ching-Ju Hsu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Mouse Model ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells ◽  
Stem Cell Therapies ◽  
Dopaminergic Cell ◽  
Cell Therapies

Parkinson’s disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

Stem Cell Therapies for the Treatment of Diabetic Neuropathies: Future Perspectives

2020 ◽  
Vol 17 (1) ◽  
pp. 2-10
Author(s):  
Camila Saggioro de Figueiredo ◽  
Luiz Carlos dos Reis
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Nerve Fibers ◽  
Diabetic Neuropathies ◽  
The Body ◽  
Diabetic Patients ◽  
Cell Transplant ◽  
Future Perspectives ◽  
Stem Cell Therapies ◽  
Cell Therapies

Background: Background: Diabetic neuropathies (DN) are the most common complications in diabetic patients, affecting about 70% of them. Patients with DN may lose sensation in certain areas of the body, facilitating the onset of foot ulcers, as well as chronic pain. This is due to the progressive degeneration of nerve fibers, demyelination, and axonopathy. Recent studies about stem cell therapies for the treatment of DN show promising potential for tissue regeneration. Results with mesenchymal stem cells derived from various organs/tissues demonstrate great therapeutic potential considering their easy obtainment, as well as their immunomodulatory and pro-regenerative effects. However, problems such as cell transplant rejection, tumor formation, transplantation safety, and effectiveness still need to be solved. Developmental biology lacks detailed insights into some aspects of cell mechanisms, like the genetic components of cell growth or differentiation. These gaps can limit a rapid advance in stem cell therapy research and put it in the future a little bit farther from the expectations that have emerged in recent media. Conclusion: In the present review, we attempt to discuss the potential of most studied types of stem cells, their application for the treatment of experimental diabetic neuropathies and associated clinical manifestations including future perspectives around these themes.

scholarly journals Adipose-Derived Stem Cells for Regenerative Wound Healing Applications: Understanding the Clinical and Regulatory Environment

2019 ◽  
Vol 40 (7) ◽  
pp. 784-799 ◽  
Author(s):  
Joshua Luck ◽  
Benjamin D Weil ◽  
Mark Lowdell ◽  
Afshin Mosahebi
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Therapeutic Potential ◽  
Donor Site ◽  
The United States ◽  
Donor Site Morbidity ◽  
Regulatory Environment ◽  
Adipose Derived Stem Cells ◽  
Cell Therapies ◽  
Legislative Framework

Abstract There is growing interest in the regenerative potential of adipose-derived stem cells (ADSCs) for wound healing applications. ADSCs have been shown to promote revascularization, activate local stem cell niches, reduce oxidative stress, and modulate immune responses. Combined with the fact that they can be harvested in large numbers with minimal donor site morbidity, ADSC products represent promising regenerative cell therapies. This article provides a detailed description of the defining characteristics and therapeutic potential of ADSCs, with a focus on understanding how ADSCs promote tissue regeneration and repair. It summarizes the current regulatory environment governing the use of ADSC products across Europe and the United States and examines how various adipose-derived products conform to the current UK legislative framework. Advice is given to clinicians and researchers on how novel ADSC therapeutics may be developed in accordance with regulatory guidelines.

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