Adipose-derived Regenerative Cells Research Articles

Hyaluronate Acid Plus Platelet-Rich Plasma Is Superior to Steroids for Pain Relief Less Than 6 Months Using Injection Therapy of Partial Rotator Cuff Tears: A Systematic Review and Network Meta-analysis

PurposeWe conducted our network meta-analysis to compare the efficacy of the steroid injections to other injectable therapies in partial-thickness rotator cuff tears (PTRCTs). MethodsA systematic literature search was performed until October 25, 2021 in three databases (CENTRAL, Embase, MEDLINE). Eligible studies compared the efficacy of steroid, hyaluronic acid (HA), platelet-rich plasma (PRP), the combination of HA and PRP (HA+PRP), and adipose-derived regenerative cells (ADRC) in RC tears. The primary outcomes were the Visual Analogue Scale (VAS), Constant Murley Score (CMS), and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form. Using paired and network meta-analysis, we calculated pooled mean differences (MDs) with 95% confidence intervals (CIs). ResultsWe included a total of seven articles in the quantitative synthesis. In shorter periods, the HA+PRP combination was superior to the other substances we investigated (HA+PRP: VAS (0-4 weeks): MD: −0.99 [CI = −1.62, −0.36]; CMS (0-3 months): 20.56 [CI = 16.18, 24.94]. This combination was followed by the use of HA or PRP alone, depending on the duration of follow-up and the outcome being studied. In our study, short-term results suggest that saline is superior to steroids for partial tears, but this trend is reversed at six-month follow-up. ConclusionOur results suggest the combination of HA and PRP to be a more effective therapeutic option for partial RC ruptures for short terms, but there is no significant difference after 6 months. Level of EvidenceII, Included of Level of Evidence studies I-II

No Clinical Efficacy of Adipose-Derived Regenerative Cells and Lipotransfer in Breast Cancer-Related Lymphedema: A double-blinded placebo-controlled phase-II trial.

Breast cancer-related lymphedema (BCRL) is a debilitating sequela affecting up to one in three breast cancer survivors. Current treatments are palliative and does not address the underlying lymphatic injury. Recently, preclinical and non-randomized studies have shown promising results using Adipose-Derived Regenerative Cells (ADRCs) and lipotransfer in alleviating BCRL through regeneration of lymphatic tissue. However no randomized controlled trial has been performed in an attempt to eliminate a placebo effect. This randomized, double-blinded, placebo-controlled trial included patients with no-option, persistent disabling unilateral BCRL. Patients were randomly assigned in a 1:1 ratio to receive either autologous ADRCs (4.20x10 7±1.75x10 7 cells) and 30cc lipotransfer or placebo (saline) to the axilla. The primary outcome was a change in BCRL volume one year after treatment. Secondary outcomes included changes in the quality of life, indocyanine green lymphangiography stage, bioimpedance, and safety. Eighty patients were included, of which 39 were allocated to ADRCs and lipotransfer treatment and 41 to placebo treatment. Baseline characteristics were similar in both groups. One year after treatment, no objective improvements were observed in the treatment or placebo groups. In contrast, significant subjective improvements were noted for both the treatment and placebo groups. This trial failed to confirm a benefit of ADRCs and lipotransfer in the treatment of BCRL. These non-confirmatory results suggest that ADRC and lipotransfer should not be recommended for alleviating BCRL at this time. However, we cannot exclude that repeated treatments or higher doses of ADRCs or lipotransfer could yield a clinical effect.

Autologous adipose tissue injection in the treatment of alopecia: A mini-review.

Alopecia may decrease patients' quality of life and self-confidence by limiting their social life. Therefore, the main goal of the treatment is to limit or halt the progression of inflammation, scarring, and hair loss. The promising effect of fat injection on hair regrowth, limited adverse effects, and subsiding inflammation can be proof of its efficacy and safety in treating alopecia. This review sought to assess the role of autologous fat tissue injection in scarring and non-scarring alopecia. Accordingly, a thorough search was performed on the Web of Science, Scopus, and PubMed/Medline databases, as well as the Google Scholar search engine, for studies published from inception until September 1st, 2023, using the related keywords. Autologous fat grafting (AFG) is a novel and potentially effective modality for treating alopecia, particularly primary and secondary cicatricial alopecia. AFG can be an effective semi-invasive option for treating refractory lichen planopilaris because it induces angiogenesis, which supports hair regrowth. In addition to cicatricial alopecia, AFG held promise for treating non-scarring alopecia, including androgenic alopecia and alopecia areata. The adipose-derived regenerative cells (ADRCs) in adipose tissue (AT) secrete different growth factors, further supporting hair regeneration. Moreover, different anti-inflammatory and anti-oxidative agents are known in AT, preventing further damage to hair follicles. AFG can significantly control inflammatory processes, improve signs and symptoms, and increase hair density and diameter.

Management of partial-thickness rotator cuff tears with autologous adipose-derived regenerative cells is safe and more effective than injection of corticosteroid

Symptomatic, partial-thickness rotator cuff tears (sPTRCT) are problematic. This study tested the hypothesis that management of sPTRCT with injection of fresh, uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) is safe and more effective than injection of corticosteroid even in the long run. To this end, subjects who had completed a former randomized controlled trial were enrolled in the present study. At baseline these subjects had not responded to physical therapy treatments for at least 6 weeks, and were randomly assigned to receive respectively a single injection of UA-ADRCs (n = 11) or a single injection of methylprednisolone (n = 5). Efficacy was assessed using the ASES Total score, pain visual analogue scale (VAS), RAND Short Form-36 Health Survey and range of motion at 33.2 ± 1.0 (mean ± SD) and 40.6 ± 1.9 months post-treatment. Proton density, fat-saturated, T2-weighted MRI of the index shoulder was performed at both study visits. There were no greater risks connected with injection of UA-ADRCs than those connected with injection of corticosteroid. The subjects in the UA-ADRCs group showed statistically significantly higher mean ASES Total scores than the subjects in the corticosteroid group. The MRI scans at 6 months post-treatment allowed to “watch the UA-ADRCs at work”.

Transplantation of Mesenchymal Stem Cells as A New Approach for Cardiovascular Diseases: from Bench to Bedside: A Perspective.

The actual therapeutic strategies opposing the cardiovascular disease (CVD) are not able to completely arrest the progression of the atherosclerotic process. Over recent years, mesenchymal stem cell (MSC) transplantation has been emerging as a safe, and promising approach to treat CVD. Of note, different types of stem cells are available, and, among them, embryonic stem cells, MSCs, induced pluripotent stem cells, endothelial progenitor cells, and adipose-derived regenerative cells are under current investigation. In the present perspective, major emphasis will be placed on MSCs for their capacity to restore heart, and artery activities.

CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects

Cellular heterogeneity represents a major challenge for regenerative treatment using freshly isolated Adipose Derived Regenerative Cells (ADRCs). Emerging data suggest superior efficacy of ADRCs as compared to the ex vivo expanded and more homogeneous ADRCs (= ASCs) for indications involving (micro)vascular deficiency, however, it remains unknown which ADRC cell subtypes account for the improvement. Surprisingly, we found regarding erectile dysfunction (ED) that the number of injected CD31+ ADRCs correlated positively with erectile function 12 months after one bolus of autologous ADRCs. Comprehensive in vitro and ex vivo analyses confirmed superior pro-angiogenic and paracrine effects of human CD31+ enriched ADRCs compared to the corresponding CD31− and parent ADRCs. When CD31+, CD31− and ADRCs were co-cultured in aortic ring- and corpus cavernous tube formation assays, the CD31+ ADRCs induced significantly higher tube development. This effect was corroborated using conditioned medium (CM), while quantitative mass spectrometric analysis suggested that this is likely explained by secretory pro-angiogenic proteins including DKK3, ANGPT2, ANAX2 and VIM, all enriched in CD31+ ADRC CM. Single-cell RNA sequencing showed that transcripts of the upregulated and secreted proteins were present in 9 endothelial ADRC subsets including endothelial progenitor cells in the heterogenous non-cultured ADRCs. Our data suggest that the vascular benefit of using ADRCs in regenerative medicine is dictated by CD31+ ADRCs.

Unlocking the Pragmatic Potential of Regenerative Therapies in Heart Failure with Next-Generation Treatments.

Patients with chronic heart failure (HF) have a poor prognosis due to irreversible impairment of left ventricular function, with 5-year survival rates <60%. Despite advances in conventional medicines for HF, prognosis remains poor, and there is a need to improve treatment further. Cell-based therapies to restore the myocardium offer a pragmatic approach that provides hope for the treatment of HF. Although first-generation cell-based therapies using multipotent cells (bone marrow-derived mononuclear cells, mesenchymal stem cells, adipose-derived regenerative cells, and c-kit-positive cardiac cells) demonstrated safety in preclinical models of HF, poor engraftment rates, and a limited ability to form mature cardiomyocytes (CMs) and to couple electrically with existing CMs, meant that improvements in cardiac function in double-blind clinical trials were limited and largely attributable to paracrine effects. The next generation of stem cell therapies uses CMs derived from human embryonic stem cells or, increasingly, from human-induced pluripotent stem cells (hiPSCs). These cell therapies have shown the ability to engraft more successfully and improve electromechanical function of the heart in preclinical studies, including in non-human primates. Advances in cell culture and delivery techniques promise to further improve the engraftment and integration of hiPSC-derived CMs (hiPSC-CMs), while the use of metabolic selection to eliminate undifferentiated cells will help minimize the risk of teratomas. Clinical trials of allogeneic hiPSC-CMs in HF are now ongoing, providing hope for vast numbers of patients with few other options available.

Prospective randomised treatment of erectile dysfunction after radical prostatectomy with autologous adipose-derived regenerative cells

Prospective randomised treatment of erectile dysfunction after radical prostatectomy with autologous adipose-derived regenerative cells

Rheumatology : what's new in 2022

In rheumatology, this year has seen an expansion of knowledge about the treatment of rheumatoid arthritis, with the availability of results from randomized trials evaluating a new molecule targeting IL-6, and regarding the safety profile of tofacitinib compared to TNF-alpha inhibitors. Interesting data on the outcome of pregnancy in patients with spondylarthritis have also been published. New molecules and different treatment strategies have shown promising results in psoriatic arthritis and systemic lupus erythematosus. The utility of botulinum toxin A injections for Raynaud's phenomenon and the efficacy of transplantation of autologous adipose-derived regenerative cells for the treatment of hand dysfunctions have been questioned by 2 randomized controlled trials of patients with systemic sclerosis.

The Composition of Adipose-Derived Regenerative Cells Isolated from Lipoaspirate Using a Point of Care System Does Not Depend on the Subject’s Individual Age, Sex, Body Mass Index and Ethnicity

Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject's individual age, sex, body mass index and ethnicity. UA-ADRCs were isolated from lipoaspirate from n = 232 subjects undergoing elective lipoplasty using the Transpose RT system (InGeneron, Inc.; Houston, TX, USA). The UA-ADRCs were assessed for the number of nucleated cells, cell viability and the number of viable nucleated cells per gram of adipose tissue harvested. Cells from n = 37 subjects were further characterized using four-channel flow cytometry. The present study shows, for the first time, that key characteristics of UA-ADRCs can be independent of the subject's age, sex, BMI and ethnicity. This result has important implications for the general applicability of UA-ADRCs in regeneration of musculoskeletal tissue. Future studies must determine whether the independence of key characteristics of UA-ADRCs of the subject's individual age, sex, BMI and ethnicity only applies to the system used in the present study, or also to others of the more than 25 different experimental methods and commercially available systems used to isolate UA-ADRCs from lipoaspirate that have been described in the literature.

RTA-dh404 decreased oxidative stress in mice ischemic limbs and augmented efficacy of therapeutic angiogenesis by intramuscular injection of adipose-derived regenerative cells in the limbs

Although an intramuscular injection of angiogenic cells to ischemic limbs with peripheral artery disease is a therapeutic option to rescue patients by augmenting neovascularization in the limbs, oxidative stress in the limbs may accelerate apoptosis of the injected cells and thereby reduce the therapeutic effect. In this study involving mice with ischemic lower limbs, whether daily oral administration of RTA-dh404, which is an activator of nuclear factor erythroid 2-related factor 2 (Nrf2) with antioxidant activity, could reduce oxidative stress in the limbs and suppress apoptosis of adipose-derived regenerative cells (ADRCs) injected in the limbs, eventually augmenting neovascularization in the limbs, was evaluated. The tissue expression of Nrf2 and concentrations of total antioxidant capacity and superoxide dismutase in the mice ischemic limbs were higher in the RTA-dh404-treated mice than in the control treated mice, and oxidative stress in the limbs of the RTA-dh404 treated mice was decreased. The day after an intramuscular injection of human ADRCs into ischemic lower limbs of immunodeficient mice, the number of apoptotic ADRCs in the ischemic limbs was decreased by approximately 25% in the RTA-dh404-treated mice compared to the control mice. Fourteen days after cell injection, neovascularization and the salvage ratio were increased by approximately 10% and 63%, respectively, in the ischemic limbs in the RTA-dh404-treated mice compared to the control mice. Pretreatment of ischemic limbs by daily oral administration of RTA-dh404 may augment the effect of therapeutic angiogenesis using an intramuscular injection of ADRCs into the ischemic limbs.

Therapeutic angiogenesis for patients with no-option critical limb ischemia by adipose-derived regenerative cells: TACT-ADRC multicenter trial.

BackgroundPatients with critical limb ischemia (CLI) still have a high rate of lower limb amputation, which is associated with not only a decrease in quality of life but also poor life prognosis. Implantation of adipose-derived regenerative cells (ADRCs) has an angiogenic potential for patients with limb ischemia.ObjectivesWe investigated safety, feasibility, and efficacy of therapeutic angiogenesis by cell transplantation (TACT) of ADRCs for those patients in multicenter clinical trial in Japan.MethodsThe TACT-ADRC multicenter trial is a prospective, interventional, open-labeled study. Patients with CLI (Fontaine class III–IV) who have no other option for standard revascularization therapy were enrolled in this study. Thirty-four target ischemic limbs of 29 patients were received freshly isolated autologous ADRCs implantation.ResultsThe overall survival rate at a post-operative period and at 6 months follow-up was 100% at any time points. As a primary endpoint for efficacy evaluation, 32 limbs out of 34 (94.1%) were free from major amputation for 6 months. Numerical rating scale (from 6 to 1) as QOL score, ulcer size (from 317 mm2 at to 109 mm2), and 6-min walking distance (from 255 to 369 m) improved in 90.6%, 83.3%, and 72.2% patients, respectively.ConclusionsImplantation of autologous ADRCs could be safe and effective for the achievement of therapeutic angiogenesis in the multicenter settings, as a result in no major adverse event, optimal survival rate, and limb salvage for patients with no-conventional option against critical limb ischemia.TRN: jRCTb040190118; Date: Nov. 24th, 2015.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10456-022-09844-7.

Stem Cell Therapy in Treating Epilepsy.

Epilepsy is a common disabling chronic neurological disorder characterized by an enduring propensity for the generation of seizures that result from abnormal hypersynchronous firing of neurons in the brain. Over 20–30% of epilepsy patients fail to achieve seizure control or soon become resistant to currently available therapies. Prolonged seizures or uncontrolled chronic seizures would give rise to neuronal damage or death, astrocyte activation, reactive oxygen species production, and mitochondrial dysfunction. Stem cell therapy is potentially a promising novel therapeutic strategy for epilepsy. The regenerative properties of stem cell-based treatment provide an attractive approach for long-term seizure control, particularly in drug-resistant epilepsy. Embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and adipose-derived regenerative cells (ADRCs) are capable of differentiating into specialized cell types has been applied for epilepsy treatment in preclinical animal research and clinical trials. In this review, we focused on the advances in stem cell therapy for epilepsies. The goals of stem cell transplantation, its mechanisms underlying graft effects, the types of grafts, and their therapeutic effects were discussed. The cell and animal models used for investigating stem cell technology in epilepsy treatment were summarized.

Direct reprogramming of adult adipose-derived regenerative cells toward cardiomyocytes using six transcriptional factors

SummaryIt is widely accepted that adipose-derived regenerative cells (ADRCs) can differentiate into mesodermal lineage cells. However, reprogramming adult ADRCs into mature cardiomyocytes is challenging. We investigated the induction of myocardial differentiation in ADRCs via direct reprogramming using lentiviral gene transfer. First, we identified candidate transcriptional factors by performing RNA sequencing and ultimately confirmed that the combination of six unique factors (Baf60c, Gata4, Gata6, Klf15, Mef2a, and Myocd) could efficiently express enhanced green fluorescent protein (GFP) in ADRCs isolated from adult alpha-myosin heavy chain promoter-driven GFP transgenic mice. The GFP-positive ADRCs induced by six factors (6F-ADRCs) expressed multiple cardiac genes and revealed cardiac differentiation in bioinformatic analysis. Moreover, injection of 6F-ADRCs into acute myocardial infarcted tissues in vivo resulted in the improvement of survival rate, fractional shortening, and reduction of infarction scar area. This study provides an alternative method for direct reprogramming of adult ADRCs into cardiomyocytes.

Adipose-derived regenerative cells as a promising therapy for cardiovascular diseases: an overview.

ABSTRACTThe number of patients with ischemic cardiovascular diseases is significantly increasing as populations age. Therapeutic angiogenesis has been developed as a new treatment strategy for such patients. In recent years, the presence of mesenchymal stem cells in adipose tissues was reported, and regenerative medicine using these cells has attracted attention worldwide. In this review, we describe how the transplantation of adipose-derived regenerative cells enhances angiogenesis and tissue regeneration because of their multilineage potential and cytokine secretion. Then, the current status of therapeutic angiogenesis using adipose-derived regenerative cells in the field of cardiovascular medicine was also described. These cells present great advantages over bone marrow mononuclear cells, as these need easier, shorter, and less invasive preparations as well as less ethical concerns and immunological problems. The efficacy of adipose-derived regenerative cell transplantation in the treatment of various diseases was examined in several clinical trials with favorable results. Currently, a multicenter study of therapeutic angiogenesis using these cells is being conducted in patients with critical limb ischemia. In conclusion, we expect that this method will soon be established as a treatment for cardiovascular diseases that have been refractory to conventional treatments.

Influence of background characteristics in responders of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence.

To determine if the male responders with post-prostatectomy incontinence in the ADRESU study, which is a clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells, are influenced by any background characteristics. Briefly, autologous adipose-derived regenerative cells isolated from abdominal adipose tissue and a mixture of adipose-derived regenerative cells with fat tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Sixteen out of 43 patients (37.2%) responded to treatment (responders) and exhibited improvement in the urine leakage volume, defined as >50% reduction from baseline determined by the 24-hour pad test at 52 weeks of treatment (or last visit within 52 weeks). Background data such as age, body weight, method of prostatectomy, baseline frequency of leaks, number of leaks, number of pad changes, International Consultation on Incontinence Questionnaire-Short Form, King's Health Questionnaire, urodynamic urethral function including functional profile length and maximum urethral closure pressure, and abdominal leak point pressure were collected and compared between responders and nonresponders. None of the background factors influenced improvement in the responders as compared with the nonresponders. However, a significant between-group difference in the rates of decrease in urine leakage volume was noted in patients of younger age (<70 years), compared with those of older age (≥70 years) from 2 to 26 weeks of treatment. A greater decrease in urine leakage volume was noted in the younger patient group than in the older patient group.

Why and how to use the body's own stem cells for regeneration in musculoskeletal disorders: a primer

BackgroundRecently, the management of musculoskeletal disorders with the patients' own stem cells, isolated from the walls of small blood vessels, which can be found in great numbers in the adipose tissue, has received considerable attention. On the other hand, there are still misconceptions about these adipose-derived regenerative cells (ADRCs) that contain vascular-associated pluripotent stem cells (vaPS cells) in regenerative medicine.MethodsBased on our previous publications on this topic, we have developed a concept to describe the significance of the ADRCs/vaPS cells in the field of orthobiologics as briefly as possible and at the same time as precisely as possible.ResultsThe ADRCs/vaPS cells belong to the group of orthobiologics that are based on autologous cells. Because the latter can both stimulate a patient’s body's localized self-healing power and provide new cells that can integrate into the host tissue during the healing response when the localized self-healing power is exhausted, this group of orthobiologics appears more advantageous than cell-free orthobiologics and orthobiologics that are based on allogeneic cells. Within the group of orthobiologics that are based on autologous cells, enzymatically isolated, uncultured ADRCs/vaPS cells have several advantages over non-enzymatically isolated cells/microfragmented fat as well as over uncultured bone marrow aspirate concentrate and cultured cells (adipose-derived stem cells, bone marrow-derived mesenchymal stem cells).ConclusionsThe use of ADRCs/vaPS cells can be seamlessly integrated into modern orthopedic treatment concepts, which can be understood as the optimization of a process which—albeit less efficiently—also takes place physiologically. Accordingly, this new safe and effective type of treatment is attractive in terms of holistic thinking and personalized medicine.

Isolation of Adipose Derived Regenerative Cells for the Treatment of Erectile Dysfunction Following Radical Prostatectomy

Stem cells are used in many research areas within regenerative medicine in part because these treatments can be curative rather than symptomatic. Stem cells can be obtained from different tissues and several methods for isolation have been described. The presented method for the isolation of adipose-derived regenerative cells (ADRCs) can be used within many therapeutic areas because the method is a general procedure and, therefore, not limited to erectile dysfunction (ED) therapy. ED is a common and serious side effect to radical prostatectomy (RP) since ED often is not well treated with conventional therapy. Using ADRC’s as treatment for ED has attracted great interest due to the initial positive results after a single injection of cells into the corpora cavernosum. The method used for the isolation of ADRC’s is a simple, automated process, that is reproducible and ensures a uniform product. Furthermore, the sterility of the isolated product is ensured because the entire process takes place in a closed system. It is important to minimize the risk of contamination and infection since the stem cells are used for injection in humans. The whole procedure can be done within 2.5-3.5 hours and does not require a classified laboratory which eliminates the need for shipping tissue to an off-site. However, the procedure has some limitations since the minimum amount of drained lipoaspirate for the isolation device to function is 100 g.

Isolation of Adipose Derived Regenerative Cells for the Treatment of Erectile Dysfunction Following Radical Prostatectomy

Stem cells are used in many research areas within regenerative medicine in part because these treatments can be curative rather than symptomatic. Stem cells can be obtained from different tissues and several methods for isolation have been described. The presented method for the isolation of adipose-derived regenerative cells (ADRCs) can be used within many therapeutic areas because the method is a general procedure and, therefore, not limited to erectile dysfunction (ED) therapy. ED is a common and serious side effect to radical prostatectomy (RP) since ED often is not well treated with conventional therapy. Using ADRC's as treatment for ED has attracted great interest due to the initial positive results after a single injection of cells into the corpora cavernosum. The method used for the isolation of ADRC's is a simple, automated process, that is reproducible and ensures a uniform product. Furthermore, the sterility of the isolated product is ensured because the entire process takes place in a closed system. It is important to minimize the risk of contamination and infection since the stem cells are used for injection in humans. The whole procedure can be done within 2.5-3.5 hours and does not require a classified laboratory which eliminates the need for shipping tissue to an off-site. However, the procedure has some limitations since the minimum amount of drained lipoaspirate for the isolation device to function is 100 g.

Abstract 13303: Identification of Critical Six Transcriptional Factors for Reprogramming of Mouse Adipose-Derived Regenerative Cells Toward Cardiomyocytes and Its Therapeutic Effect

Background: Adipose-derived regenerative cells (ADRCs) are promising stem cells for regenerative medicine that are easy to harvest from adipose tissues and can expand in vitro . While ADRCs can differentiate into mesodermal lineage cells including adipocytes, osteocytes, and chondrocytes, little is known about differentiating adult ADRCs into mature cardiomyocytes. Objective: The aim of this study was to explore how to differentiate adult mouse ADRCs into cardiomyocytes efficiently and test their effect on the myocardial infarction mouse model in vivo . Method and Results: We performed differential expression analysis to identify transcriptional factors which were upregulated in developing mice heart (E11.5) compared with ADRCs. We systemically screened the combinations of the required transcription factors in ADRCs derived from αMHC-EGFP reporter mice. Here, we identified the following six genes; Baf60c , Gata4 , Gata6 , Klf15 , Mef2a , Myocd , not more or less, as the best combination to efficiently induce αMHC in ADRCs. Fluorescence-activated cell sorting analysis showed that 3.0±0.61% (n=3) ADRCs were positive for αMHC after introducing these six factors. In addition, quantitative PCR demonstrated that several other marker genes of mature cardiomyocytes, including Actc1 , Tnnt2 , Ttn , Fhod3 , were confirmed to be upregulated by six factors. Immunocytochemical staining showed that most of the induced ADRCs had fibrous conformation of sarcomeric α-actin. Moreover, the gene expression pattern of the cells showed upregulation of genes associated with cardiac muscle cell differentiation. Finally, injection of the induced ADRCs into acute myocardial infarction lesions in vivo resulted in the improvement of survival rate (p=0.028, n=32), fractional shortening (p=0.012, n=7, 15), and the reduction of infarction scar area compared to the injection of ADRCs without induction (p=0.029, n=7). The induced ADRCs could survive in situ and continued to express the cardiac troponin T protein for four weeks after injection. Conclusions: The combination of six transcriptional factors could induce cardiomyocyte-like gene expression patterns on adult ADRCs. The induced ADRCs could have a therapeutic effect on an experimental ischemic heart model in vivo .