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.

Adipose-Based Therapies for Knee Pain—Fat or Fiction

2018 ◽  
Vol 32 (01) ◽  
pp. 055-064 ◽  
Author(s):  
Yoshiharu Shimozono ◽  
Lisa Fortier ◽  
Donald Brown ◽  
John Kennedy
Keyword(s):  
Stem Cells ◽  
Adverse Reactions ◽  
Therapeutic Potential ◽  
Stromal Vascular Fraction ◽  
The United States ◽  
Adipose Derived Stem Cells ◽  
Cell Therapies ◽  
Knee Oa ◽  
Chondrogenic Potential ◽  
Enzymatic Isolation

AbstractRegenerative cell therapies are emerging as promising treatments for numerous musculoskeletal conditions, including knee osteoarthritis (OA). Adipose-derived stem cells and possibly other adipose-based therapies have a greater chondrogenic potential than stem cells derived from bone marrow, and thus a lot of attention is being placed on them as potential regenerative agents in the treatment of knee OA. Several types of adipose-based therapies have good basic science and preclinical data supporting their translation to human therapeutic intervention. Cultured, adipose-derived stem cells appear to be good source of bioactive cells with convenient accessibility, relative abundance, and well-documented regenerative capacity. Non-culture expanded adipose-based therapy, in the forms of stromal vascular fraction and most recently micronized adipose tissue (MAT), have been utilized in patients to treat OA and other cartilage abnormalities with encouraging preliminary data. These adipose-based therapies have shown a lot of therapeutic potential; however, because of the regulatory restrictions on enzymatic isolation and cell expansion, only MAT is currently available in clinical practice in the United States. While no serious adverse reactions have been reported, adipose-derived therapies also have the potential for adverse reactions including inflammation and infection. The current review provides an update on the latest research and presents this evidence on the therapeutic potential of adipose-based therapies in the treatment of knee OA.

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.

scholarly journals Deciphering the Emerging Roles of Adipocytes and Adipose-Derived Stem Cells in Fat Transplantation

2021 ◽  
Vol 30 ◽  
pp. 096368972199779
Author(s):  
Yi Yi ◽  
Weijie Hu ◽  
Chongru Zhao ◽  
Min Wu ◽  
Hong Zeng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipogenic Differentiation ◽  
Donor Site ◽  
Donor Site Morbidity ◽  
Adipose Derived Stem Cells ◽  
Multilineage Differentiation ◽  
Fat Transplantation ◽  
Autologous Fat Transplantation ◽  
Essential Components ◽  
Tissue Defects

Autologous fat transplantation is widely regarded as an increasingly popular method for augmentation or reshaping applications in soft tissue defects. Although the fat transplantation is of simple applicability, low donor site morbidity and excellent biocompatibility, the clinical unpredictability and high resorption rates of the fat grafts remain an inevitable problem. In the sites of fat transplantation, the most essential components are the adipocyte and adipose-derived stem cells (ADSCs). The survival of adipocytes is the direct factor determining fat retention. The efficacy of fat transplantation is reduced by fat absorption and fibrosis due to the inadequate blood flow, adipocyte apoptosis and fat necrosis. ADSCs, a heterogeneous mixture of cells in adipose tissue, are closely related to tissue survival. ADSCs exhibit the ability of multilineage differentiation and remarkable paracrine activity, which is crucial for graft survival. This article will review the recent existing research on the mechanisms of adipocytes and ADSCs in fat transplantation, especially including adipocyte apoptosis, mature adipocyte dedifferentiation, adipocyte browning, ADSCs adipogenic differentiation and ADSCs angiogenesis. The in-depth understanding of the survival mechanism will be extremely valuable for achieving the desired filling effects.

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 Therapeutic Potential of Magnetic Nanoparticle-Based Human Adipose-Derived Stem Cells in a Mouse Model of Parkinson’s Disease

2021 ◽  
Vol 22 (2) ◽  
pp. 654
Author(s):  
Ka Young Kim ◽  
Keun-A Chang
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Magnetic Nanoparticles ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Magnetic Nanoparticle ◽  
Imaging System ◽  
Therapeutic Potential ◽  
Adipose Derived Stem Cells

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Several treatments for PD have focused on the management of physical symptoms using dopaminergic agents. However, these treatments induce various adverse effects, including hallucinations and cognitive impairment, owing to non-targeted brain delivery, while alleviating motor symptoms. Furthermore, these therapies are not considered ultimate cures owing to limited brain self-repair and regeneration abilities. In the present study, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASCs) using magnetic nanoparticles in a 6-hydroxydopamine (6-OHDA)-induced PD mouse model. We used the Maestro imaging system and magnetic resonance imaging (MRI) for in vivo tracking after transplantation of magnetic nanoparticle-loaded hASCs to the PD mouse model. The Maestro imaging system revealed strong hASCs signals in the brains of PD model mice. In particular, MRI revealed hASCs distribution in the substantia nigra of hASCs-injected PD mice. Behavioral evaluations, including apomorphine-induced rotation and rotarod performance, were significantly recovered in hASCs-injected 6-OHDA induced PD mice when compared with saline-treated counterparts. Herein, we investigated whether hASCs transplantation using magnetic nanoparticles recovered motor functions through targeted brain distribution in a 6-OHDA induced PD mice. These results indicate that magnetic nanoparticle-based hASCs transplantation could be a potential therapeutic strategy in PD.

Prospective application of exosomes derived from adipose‐derived stem cells in skin wound healing: A review

2019 ◽  
Vol 19 (3) ◽  
pp. 574-581 ◽  
Author(s):  
He Qiu ◽  
Shuo Liu ◽  
Kelun Wu ◽  
Rui Zhao ◽  
Lideng Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Skin Wound ◽  
Adipose Derived Stem Cells ◽  
Skin Wound Healing ◽  
Prospective Application

scholarly journals Therapeutic potential of adipose-derived stem cells and macrophages for ischemic skeletal muscle repair

2017 ◽  
Vol 12 (2) ◽  
pp. 153-167 ◽  
Author(s):  
Viktoriya Rybalko ◽  
Pei-Ling Hsieh ◽  
Laura M Ricles ◽  
Eunna Chung ◽  
Roger P Farrar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Therapeutic Potential ◽  
Adipose Derived Stem Cells ◽  
Muscle Repair

Extracellular vesicles derived from adipose-derived stem cells accelerate diabetic wound healing by suppressing the expression of matrix metalloproteinase-9

2021 ◽  
Vol 22 ◽  
Author(s):  
Jiang-wen Wang ◽  
Yuan-zheng Zhu ◽  
Xuan Hu ◽  
Jia-ying Nie ◽  
Zhao-hui Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mouse Model ◽  
Adipose Derived Stem Cells ◽  
Collagen Deposition ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds ◽  
Metalloproteinase 9

Background: The healing of diabetic wounds is poor due to a collagen deposition disorder. Matrix metalloproteinase-9 (MMP-9) is closely related to collagen deposition in the process of tissue repair. Many studies have demonstrated that extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) promote diabetic wound healing by enhancing collagen deposition. Objective: In this study, we explored if ADSC-EVs could downregulate the expression of MMP-9 in diabetic wounds and promote wound healing by improving collagen deposition. The potential effects of ADSC-EVs on MMP-9 and diabetic wound healing were tested both in vitro and in vivo. Methods: We first evaluated the effect of ADSC-EVs on the proliferation and MMP-9 secretion of HaCaT cells treated with advanced glycation end product-bovine serum albumin (AGE-BSA), using CCK-8 western blot and MMP-9 enzyme-linked immunosorbent assay(ELISA). Next, the effect of ADSC-EVs on the healing, re-epithelialisation, collagen deposition, and MMP-9 concentration in diabetic wound fluids was evaluated in an immunodeficient mouse model via MMP-9 ELISA and haematoxylin and eosin, Masson’s trichrome, and immunofluorescence staining for MMP-9. Results: In vitro, ADSC-EVs promoted the proliferation and MMP-9 secretion of HaCaT cells.In vivo, ADSC-EVs accelerated diabetic wound healing by improving re-epithelialisation and collagen deposition and by inhibiting the expression of MMP-9. Conclusion: ADSC-EVs possessed the healing of diabetic wounds in a mouse model by inhibiting downregulating MMP-9 and improving collagen deposition.Thus ,ADSC-EVs are a promising candidate for the treatment of diabetic wounds .

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