Therapeutic Effects Of Adipose-derived Stem Cells Research Articles

Adipose-derived stem cells apoptosis rejuvenate radiation-impaired skin in mice via remodeling and rearranging dermal collagens matrix

BackgroundChronic radiation dermatitis (CRD) is a late consequence of radiation with high incidence in patients receiving radiotherapy. Conventional therapies often yield unsatisfactory results. Therefore, this study aimed to explore the therapeutic potential and mechanism of adipose-derived stem cells (ADSCs) for CRD, paving the way for novel regenerative therapies in clinical practice.MethodsClinical CRD skin biopsies were analyzed to character the pathological changes of CRD skin and guided the animal modeling scheme. Subsequently, an in vivo analysisusing mouse CRD models was conducted to explore their effects of ADSCs on CRD, monitoring therapeutic impact for up to 8 weeks. Transcriptome sequencing and histologic sections analysis were performed to explore the potential therapeutic mechanism of ADSCs. Following observing extensive apoptosis of transplanted ADSCs, the therapeutic effect of ADSCs were compared with those of apoptosis-inhibited ADSCs. Multiphoton imaging and analysis of collagen morphologic features were employed to explain how translated ADSCs promote collagen remodeling at the microscopic level based on the contrast of morphology of collagen fibers.ResultsFollowing injection into CRD-afflicted skin, ADSCs therapy effectively mitigated symptoms of CRD, including acanthosis of the epidermis, fibrosis, and irregular collagen deposition, consistent with the possible therapeutic mechanism suggested by transcriptome sequencing. Notably, in vivo tracking revealed a significant reduction in ADSCs number due to extensive apoptosis. Inhibiting apoptosis in ADSCs partially tempered their therapeutic effects. Mechanically, analysis of collagen morphologic features indicated that translated ADSCs might promote dermal extracellular matrix remodeling through enlarging, lengthening, crimping, and evening collagen, counteracting the atrophy and rupture caused by irradiation.ConclusionsThis study demonstrated that ADSCs underwent substantial apoptosis upon local skin transplantation, and paradoxically, this apoptosis is essential for their efficacy in promoting the regeneration of late radiation-impaired skin. Mechanically, transplanted ADSCs could promote the remodeling and rearrangement of radiation-damaged dermal collagen matrix.

Synovial Fluid Derived from Human Knee Osteoarthritis Increases the Viability of Human Adipose-Derived Stem Cells through Upregulation of FOSL1

Knee osteoarthritis (Knee OA) is an irreversible condition that causes bone deformity and degeneration of the articular cartilage that comprises the joints, resulting in chronic pain and movement disorders. The administration of cultured adipose-derived stem cells (ADSCs) into the knee joint cavity improves the clinical symptoms of Knee OA; however, the effect of synovial fluid (SF) filling the joint cavity on the injected ADSCs remains unclear. In this study, we investigated the effect of adding SF from Knee OA patients to cultured ADSCs prepared for therapeutic use in an environment that mimics the joint cavity. An increase in the viability of ADSCs was observed following the addition of SF. Gene expression profiling of SF-treated ADSCs using DNA microarrays revealed changes in several genes involved in cell survival. Of these genes, we focused on FOSL1, which is involved in the therapeutic effect of ADSCs and the survival and proliferation of cancer stem cells. We confirmed the upregulation of FOSL1 mRNA and protein expression using RT-PCR and western blot analysis, respectively. Next, we knocked down FOSL1 in ADSCs using siRNA and observed a decrease in cell viability, indicating the involvement of FOSL1 in the survival of ADSCs. Interestingly, in the knockdown cells, ADSC viability was also decreased by SF exposure. These results suggest that SF enhances cell viability by upregulating FOSL1 expression in ADSCs. For therapy using cultured ADSCs, the therapeutic effect of ADSCs may be further enhanced if an environment more conducive to the upregulation of FOSL1 expression in ADSCs can be established.

Treatment of “En Coupe De Sabre “ Linear Scleroderma. Soft Tissue Augmentation and Regeneration by Autologous Fat Transfer

Aim: Frontal linear scleroderma, also known as ‘‘en coup de sabre,’’ is a congenital deformity characterized by atrophy and furrowing of the skin of the front parietal area above the level of the eyebrows. In most cases it occurs as a single paramedian line that may be associated with hypoplasia of underlying structures and facial hemiatrophy. In case of a wide lesion many reconstructive strategies have been proposed. The modern approach is aimed at augmentation of the tissue deficiency by using lipostructure and tissue regeneration. Autologous fat transfer (AFT) seems to be an effective strategy to restore the normal volume and contour of the face while providing a source of adipose-derived stem cells (ADSCs) with a multilineage differentiation potential. Methods: In this report, we present a rare case of linear scleroderma en coupe de sabre which was successfully managed with three stages of autologous fat grafting. Conclusion: The proposed uses for ADSCs in tissue repair and regeneration are quite impressive. Recent works on ADSCs would suggest that adult cells may prove to be an equally powerful regenerative tool in treating congenital and acquired maxillofacial disorders. More importantly, physicians, researchers and international associations need to cooperate in informing clinicians about what practices are based on evidence and to encourage support of additional research. There is increasing interest in a possible therapeutic effect of ADSCs from processed lipoaspirate for a wide spectrum of clinical applications in the facial and craniofacial area. AFT can be used in any facial area where soft tissue is lacking or where there is scarring, producing natural and long-lasting results. Mesenchymal stem cells represent a great tool in regenerative medicine. However, more definitive studies are needed to answer specific questions regarding the best technique to be used and the role of ADSCs. Autologous fat grafting provides a safe and easy approach for the treatment of linear scleroderma en coup de sabre, long-term clinically satisfactory results can be obtained.

Research on treating atherosclerotic erectile dysfunction by magnetic adipose-derived stem cells

Objective To explore the effect of magnetic adipose-derived stem cells(ADSCs) on treating atherosclerotic erectile dysfunction(ASED). Methods ADSCs were extracted from para-epididymis fat of SD rats aged 2 to 3 months for culture and identification. ADSCs were labeled with the magnetic resonance contrast agent superparamagnetic iron oxide nanoparticles(SPIONs). Meanwhile, the labeling efficiency, as well as effect on cell viability and proliferation was evaluated using Prussian blue, trypan blue staining and MTT method. The paramagnetism of ADSCs after SPIONs labeling was evaluated through the action of the exterior magnetic field. The atherosclerosis rat model was constructed, and ADSCs were injected into the corpus cavernosum afterwards. Intracorporeal pressure(ICP) was determined in the normal group, atherosclerosis group, ADSCs treatment with no action of magnetic field group, and ADSCs treatment with action of exterior magnetic field group after 4 weeks.Contents of smooth muscle and endothelium in corpus cavernosum of rats were detected using immunohistochemical staining. In addition, SOD and NOS activities, as well as MDA content were detected by ELISA. Results ADSCs extracted from para-epididymis fat of rats had grown actively and had high purity. Besides, they showed multi-lineage differentiation. SPIONs could be effectively absorbed by ADSCs, which would not remarkably inhibit the proliferation and cell viability of ADSCs. Iron content in cell was positively correlated with the iron concentration in the labeled SPIONs, and ADSCs showed paramagnetism after SPIONs labeling. ADSCs transplantation could notably improve the erectile function of ASED rats and enhanced the endothelium and smooth muscle contents in corpus cavernosum. Moreover, it could also correct the oxidative stress state in corpus cavernosum tissue, and some ADSCs had differentiated into smooth muscle and endothelial cells. Conclusions ADSCs transplantation can markedly improve the erectile function of ASED rats. Furthermore, magnetic induction has promoted the colonization of ADSCs in the corpus cavernosum, which contributes to enhancing the therapeutic effect of ADSCs and provides a new thinking and concept for stem cell therapy. Key words: Plaque, Atherosclerotic; Erectile Dysfunction; Mesenchymal Stem Cells

Pretreatment of Diabetic Adipose-derived Stem Cells with mitoTEMPO Reverses their Defective Proangiogenic Function in Diabetic Mice with Critical Limb Ischemia

Adipose-derived stem cells (ADSCs) have the ability to migrate to injury sites and facilitate tissue repair by promoting angiogenesis. However, the therapeutic effect of ADSCs from patients with diabetes is impaired due to oxidative stress. Given that diabetes is a group of metabolic disorders and mitochondria are a major source of reactive oxygen species (ROS), it is possible that mitochondrial ROS plays an important role in the induction of diabetic ADSC (dADSC) dysfunction. ADSCs isolated from diabetic mice were treated with mitoTEMPO, a mitochondrial ROS scavenger, or TEMPO, a universal ROS scavenger, for three passages. The results showed that pretreatment with mitoTEMPO increased the proliferation, multidifferentiation potential, and the migration and proangiogenic capacities of dADSCs to levels similar to those of ADSCs from control mice, whereas pretreatment with TEMPO showed only minor effects. Mechanistically, mitoTEMPO pretreatment enhanced the mitochondrial antioxidant capacity of dADSCs, and knockdown of superoxide dismutase reduced the restored mitochondrial antioxidant capacity and attenuated the proangiogenic effects induced by mitoTEMPO pretreatment. In addition, mitoTEMPO pretreatment improved the survival of dADSCs in diabetic mice with critical limb ischemia, showing protective effects similar to those of control ADSCs. Pretreatment of dADSCs with mitoTEMPO decreased limb injury and improved angiogenesis in diabetic mice with critical limb ischemia. These findings suggested that short-term pretreatment of dADSCs with a mitochondrial ROS scavenger restored their normal functions, which may be an effective strategy for improving the therapeutic effects of ADSC-based therapies in patients with diabetes.

Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia.

Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent therapeutic cocktail for patients with CLI, many of whom are at risk for amputation of the affected limb.