Adipose Tissue-derived Regenerative Cells Research Articles

Safety and Efficacy of Autologous Stem Cell Treatment for Facetogenic Chronic Back Pain.

Chronic back pain due to facet joint syndrome is a common and debilitating condition. Advances in regenerative medicine have shown that autologous unmodified adipose tissue-derived regenerative cells (ADRC) provide several beneficial effects. These regenerative cells can differentiate into various tissues and exhibit a strong anti-inflammatory potential. ADRCs can be obtained from a small amount of fatty tissue derived from the patient's abdominal fat. We report long-term results of 37 patients (age 31-78 years, mean 62.5) suffering from "Facet Joint Syndrome" The pathology was confirmed by clinical, radiological examinations and fluoroscopically guided test injections. Then, liposuction was performed. An amount of 50-100 cc of fat was harvested. To recover stem cells from adipose tissue, we use the CE-certified Transpose RT™ system from InGeneron GmbH. The cells were then injected under fluoroscopic control in the periarticular fat. Follow-up examinations were performed at 1 week, 1 year, and 5 years. Every patient reported improved VAS pain at any follow-up (1 week, 1 year, and 5 years) with ADRCs compared to the baseline. Our observational data indicate that facet joint syndrome patients treated with unmodified adipose tissue-derived regenerative cells experience improved the quality of life in the long term.

Knee meniscus regeneration using autogenous injection of uncultured adipose tissue-derived regenerative cells.

IntroductionThe low healing potential of mature menisci necessitates traditional surgical removal (meniscectomy) to eliminate acute or chronic degenerative tears. However, removal of meniscal tissue is main factor causing osteoarthritis. Adipose tissue-derived regenerative cells (ADRCs), a heterogeneous cell population that includes multipotent adipose-derived stem cells and other progenitor cells, were easily isolated in large amounts from autologous adipose tissue, and same-day processing without culture or expansion was possible. This study investigated the regenerative potential of autologous ADRCs for use in meniscus defects.MethodsIn 10- to 12-week-old male SD rat partial meniscectomy model, an atelocollagen sponge scaffold without or with ADRCs (5.0 × 105 cells) was injected into each meniscus defect. Reconstructed menisci were subjected to histologic, and dynamic mechanical analyses.ResultsAfter 12 weeks, areas of regenerated meniscal tissue in the atelocollagen sponge scaffold in rats with ADRCs (64.54 ± 0.52%, P < 0.05, n = 10) were larger than in those without injection (57.96 ± 0.45%). ADRCs were shown capable of differentiating chondrocyte-like cells and meniscal tissue components such as type II collagen. Higher elastic moduli and lower fluid permeability of regenerated meniscal tissue demonstrated a favorable structure-function relationship required for native menisci, most likely in association with micron-scale porosity, with the lowest level for tissue integrity possibly reproducible.ConclusionsThis is the first report of meniscus regeneration induced by injection of ADRCs. The results indicate that ADRCs will be useful in future clinical cell-based therapy strategies, including as a cell source for reconstruction of damaged knee menisci.

Adipose tissue-derived regenerative cells improve implantation of fertilized eggs in thin endometrium.

Aim: Embryo implantation and subsequent pregnancy depends on endometrial thickness. To investigate potential fertility strategies for women with thin endometrium, we explored the efficacy of adipose tissue-derived regenerative cells (ADRCs) on thin endometrium and embryo implantation in a mouse model. Materials & methods: ADRCs isolated from mouse subcutaneous fat were characterized by flow cytometry. Endometrium thickness, endometrial fibrosis, embryo implantation and angiogenesis factors were evaluated in uterine cavities of ethanol-induced thin endometrium mice with ADRC transplantation. Results: ADRCs included adipose-derived stem cells and some blood vessel component cells. ADRCs improved endometrial thickness, endometrial fibrosis and embryo implantation and augmented vascular endothelial growth factor expression in the mouse uterine. Conclusion: ADRCs may be a useful therapeutic strategy to improve fertility of women with thin endometrium.

Pioglitazone strengthen therapeutic effect of adipose-derived regenerative cells against ischemic cardiomyopathy through enhanced expression of adiponectin and modulation of macrophage phenotype

BackgroundThe efficacy of cell transplantation in heart failure is reportedly modest, but adjuvant drugs combined with cell therapy may improve this efficacy. Peroxisome proliferator-activated receptor (PPAR)γ, one of the hypoglycemic medicine for diabetes mellitus, reportedly enhances cytokine production in adipose tissue-derived regenerative cells (ADRCs). We hypothesized that combined administration of PPARγ agonists and ADRCs may enhance the paracrine effects of adiponectin (APN), leading to functional recovery in a chronic myocardial infarction (MI) model.MethodsADRCs were isolated from adipose tissues of adult rats by gradient centrifugation and embedded in bio-compatible fibrin-glue to produce ADRCs grafts. In the in vitro study, the ADRCs grafts released APN, which was significantly enhanced by the PPARγ agonist (PGZ, pioglitazone). Transplantation of ADRCs grafts (group A), ADRCs mixed with PGZ (group AP), APN knockdown-ADRCs (group Si) or PGZ (group P) onto the epicardium or a sham operation (group C) was performed (n = 10–20 per group).ResultsThe AP group showed significant improvement in ejection fraction compared to that in the other groups. In the AP group, a significantly larger number of M2-polarized macrophages was detected and existed for a significantly longer duration in the infarct area. Furthermore, comparing Si group and P group, western blotting of T-cadherin revealed that exogenous APN and local expression of T-cadherin were essential to this histological change and recovery of cardiac function.ConclusionsCombined administration of PPARγ agonist and ADRSCs activated M2-polarized macrophages with enhancement of APN paracrine effects and lead to better cardiac function in a rat infarction model.

Intraspinal Transplantation of the Adipose Tissue-Derived Regenerative Cells in Amyotrophic Lateral Sclerosis in Accordance with the Current Experts' Recommendations: Choosing Optimal Monitoring Tools.

Stem cells (SCs) may constitute a perspective alternative to pharmacological treatment in neurodegenerative diseases. Although the safety of SC transplantation has been widely shown, their clinical efficiency in amyotrophic lateral sclerosis (ALS) is still to be proved. It is not only due to a limited number of studies, small treatment groups, and fast but nonlinear disease progression but also due to lack of objective methods able to show subtle clinical changes. Preliminary guidelines for cell therapy have recently been proposed by a group of ALS experts. They combine clinical, neurophysiological, and functional assessment together with monitoring of the cytokine level. Here, we describe a pilot study on transplantation of autologous adipose-derived regenerative cells (ADRC) into the spinal cord of the patients with ALS and monitoring of the results in accordance with the current recommendations. To show early and/or subtle changes within the muscles of interest, a wide range of clinical and functional tests were used and compared in order to choose the most sensitive and optimal set. Additionally, an analysis of transplanted ADRC was provided to develop standards ensuring the derivation and verification of adequate quality of transplanted cells and to correlate ADRC properties with clinical outcome.

Regeneration of knee meniscus damages by transplanting adipose tissue-derived regenerative cells

Regeneration of knee meniscus damages by transplanting adipose tissue-derived regenerative cells

VEGF secretion by adipose tissue-derived regenerative cells is impaired under hyperglycemic conditions via glucose transporter activation and ROS increase.

Transplantation of cultured adipose-derived regenerative cells (ADRCs) into ischemic tissues promotes neovascularization and blood perfusion recovery. These effects are attenuated in diabetes patients. We examined the effects of hyperglycemia on the angiogenic capacity of ADRCs derived from Wistar rats both in vivo and in vitro. Cultured ADRCs were predominantly composed of CD90 positive cells; prevalence of CD90 positive cells was not affected by hyperglycemia. mRNA and protein levels of vascular endothelial growth factor (VEGF) were significantly decreased in ADRCs under hyperglycemic conditions independent of osmolarity, whereas mRNA levels of hepatocyte growth factor and fibroblast growth factor were unaffected. Since ADRCs express glucose transporter proteins GLUT1, 3 and 4, we examined the effects of the glucose transporter inhibitor phloretin on reactive oxygen species (ROS) and angiogenic factors. Phloretin decreased the glucose uptake rate, reduced ROS, and increased VEGF mRNA in ADRCs exposed to a hyperglycemic condition. In vivo transplantation of ADRCs cultured under hyperglycemic conditions into mouse ischemic limbs resulted in significantly decreased blood perfusion and capillary density in ischemic regions compared with transplantation of ADRCs cultured under normoglycemic conditions. These results suggest that hyperglycemia impaired VEGF production in ADRCs via an increase of ROS, impairing the angiogenic capacity of ADRCs transplanted into ischemic limbs.

Transplantation of freshly isolated adipose tissue-derived regenerative cells enhances angiogenesis in a murine model of hind limb ischemia

Therapeutic angiogenesis has emerged as one of the most promising therapies for severe ischemic cardiovascular diseases with no optional therapy. Several investigators have reported that transplantation of cultured adipose-derived regenerative cells (cADRCs) to ischemic tissues promotes neovascularization and blood perfusion recovery; however, cell therapy using cultured cells has several restrictions. To resolve this problem, the angiogenic capacity of freshly isolated ADRCs (fADRCs) obtained from Lewis rats was compared with cADRCs, both in vivo and in vitro. Flow cytometric analysis showed that fADRCs contained several cell types such as endothelial progenitor cells and endothelial cells; however, these cells were present in a very small proportion in cADRCs. Transplantation of fADRCs in mice significantly improved blood perfusion, capillary density, and production of several angiogenic factors in transplanted ischemic limbs compared with a saline-injected group, whereas these effects were not observed in the cADRCs-injected group. fADRCs also showed significantly higher expression levels of angiogenic factors than cADRCs in the in vitro study. Furthermore, fADRC stimulated tube formation more remarkably than cADRC in an in vitro tube formation assay. These results suggested that fADRCs have an effective angiogenic capacity, and they would be more valuable as a source for cell-based therapeutic angiogenesis than cADRCs or other stem/progenitor cells.

Promotion of skeletal muscle repair in a rat skeletal muscle injury model by local injection of human adipose tissue-derived regenerative cells

Human adipose tissue-derived regenerative cells (ADRCs) can be isolated easily and aseptically from unwanted subcutaneous fat without culturing. ADRCs have been used in clinical cosmetic therapy. In addition, they are expected to be an attractive and feasible source of cell-based therapies in regenerative medicine. Therefore, this paper investigates whether transplantation of human adult ADRCs into skeletal muscle injury models promotes the repair of muscle tissues. This was done by locally injecting human ADRCs into an injured site after laceration of the nude-rat tibialis anterior muscle. Phosphate-buffered saline (PBS) and bone marrow mononuclear cells (MNCs) were injected as negative and positive controls, respectively. After injury, recovery of muscle strength was accelerated by transplantation of ADRCs compared to administration of PBS and MNCs. Moreover, transplantation of ADRCs also enhanced angiogenesis and myogenesis, but the number of vascular and muscular cells labeled with the human cell-specific maker was limited at the injury site. Results showed that transplantation of ADRCs into a skeletal muscle injury model promoted repair of muscle tissues in a paracrine manner rather than differentiation of itself into blood vessels and myofibres. Thus, it is believed that ADRCs are a useful and feasible cell source not only for cosmetic therapy but also for regenerative therapy.

Periurethral injection of autologous adipose‐derived regenerative cells for the treatment of male stress urinary incontinence: Report of three initial cases

To report a novel cell therapy using autologous adipose tissue-derived regenerative cells for male stress urinary incontinence caused by urethral sphincteric deficiency, and the outcomes in the initial cases undergoing periurethral injection of adipose tissue-derived regenerative cells. Three patients with moderate stress incontinence after radical prostatectomy and holmium laser enucleation of the prostate were enrolled. Adipose tissue-derived regenerative cells were isolated from the abdominal adipose tissue by using the Celution system. Subsequently, the isolated adipose tissue-derived regenerative cells, and a mixture of adipose tissue-derived regenerative cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Short-term outcomes during a 6-month follow up were assessed by a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography and magnetic resonance imaging. Urinary incontinence progressively improved after 2 weeks of injection up to 6 months in terms of decreased leakage volume, decreased frequency and amount of incontinence, and improved quality of life. Both maximum urethral closing pressure and functional profile length increased. Magnetic resonance imaging suggested a sustained presence of the injected adipose tissue. Enhanced ultrasonography showed a progressive increase in the blood flow to the injected area. No significant adverse events were observed peri- and postoperatively. These preliminary findings suggest that periurethral injection of the autologous adipose tissue-derived regenerative cells is a safe and feasible treatment modality for male stress urinary incontinence.

2010 ArgoSpine Thesis Award

The research presented in this thesis actually comprises of two parts: in the first part a new intervertebral disc degeneration model was developed and in the second par t this model was used to evaluate the regenerative potential of adipose tissue-derived regenerative cells directly injected into the disc in a one-step procedure.