• Administration routes
• Clinical trial
• Heart diseases
• Mesenchymal stem cells
• Optimal doses

• Heart failure
• ischemic cardiomyopathy
• mesenchymal stem cells
• non-ischemic dilated cardiomyopathy
• regenerative medicine
• survival analysis

• Humans
• Male
• Female
• Cardiomyopathies/therapy
• Cardiomyopathies/mortality
• Middle Aged
• Aged
• Cell- and Tissue-Based Therapy/methods
• Disease-Free Survival
• Cohort Studies
• Mesenchymal Stem Cell Transplantation
• Kaplan-Meier Estimate

• 1R01 HL137355 NIH HHS
• 1R01 HL107110 NIH HHS
• 1R01 HL134558 NIH HHS
• 5R01 CA136387 NIH HHS
• 5UM1 HL113460 NIH HHS

• Atherosclerosis
• Bibliometrics
• CiteSpace
• Treatment strategy
• Visual analysis

• clinical translation
• exosomes
• good manufacturing practice
• mesenchymal stem cells
• therapeutic products

• Humans
• Exosomes
• Cell Differentiation
• Mesenchymal Stem Cells
• Stem Cells
• Cell Proliferation

• 2022YFA1105600 National Key Research and Development Program of China
• 5001- 4001010 Start-up Grant for Stem Cell and Regenerative Medicine
• JCYJ20210324114606019 Shenzhen Science and Technology Program
• 06172956 Hong Kong Health and Medical Research Fund (HMRF)
• R7036-21 Hong Kong the Impact Research Fund

• endothelial dysfunction
• endothelium
• heart failure
• inflammation
• nitric oxide

• cellular therapy
• good manufacturing practice
• mesenchymal stromal cells
• myelination
• olfactory mucosa-derived

• Humans
• Culture Techniques
• Anti-Bacterial Agents
• Axons
• Biological Transport
• Mesenchymal Stem Cells

• TCS/19/22 Chief Scientist Office
• MR/V00381x/1 Medical Research Council

• allogeneic
• cell-based therapy
• in vivo
• mesenchymal stem cells
• regenerative medicine
• transplant

• Humans
• Transplantation, Homologous
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells
• Cell- and Tissue-Based Therapy
• Hematopoietic Stem Cell Transplantation

• Allogeneic
• Human umbilical cord
• Infusion
• Mesenchymal stem cells
• Vital signs

• Dilated cardiomyopathy
• IGFBP2
• Left ventricular ejection fraction
• Machine learning
• RNA modifications

• Humans
• Biomarkers
• Cardiomyopathy, Dilated/genetics
• Cardiomyopathy, Dilated/diagnosis
• Endothelial Cells
• Insulin-Like Growth Factor Binding Protein 2
• RNA
• Stroke Volume
• Ventricular Dysfunction, Left/genetics
• Ventricular Function, Left

• 82170445 National Natural Science Foundation of China

• cell-based therapy
• female sexual dysfunction
• mesenchymal stem cells
• regenerative medicine
• restorative therapy
• stem cell therapy

• Female
• Humans
• Sexual Dysfunctions, Psychological/therapy
• Sexual Dysfunction, Physiological
• Quality of Life
• Sexual Behavior
• Women's Health

• R01 HL134558 NHLBI NIH HHS
• R01 HL134558 NIH HHS
• National Institutes of Health

• heart failure
• mesenchymal cells
• mesoblast
• myocardial regeneration
• reduced ejection fraction
• stem cell
• stem cell therapy

• Humans
• Stroke Volume
• Mesenchymal Stem Cell Transplantation
• Heart Failure/therapy
• Chronic Disease
• Ventricular Dysfunction, Left

• R01 HL134558 NHLBI NIH HHS
• 1R01HL134558 NHLBI NIH HHS
• Congressionally Directed Medical Research Programs
• National Heart, Lung, and Blood Institute

• disease modelling
• endothelial dysfunction (ED)
• genetic cardiomyopathies
• hiPSC-derived endothelial cells (hiPSC-ECs)
• human induced pluripotent stem cells (hiPSCs)
• personalized medicine

• Fondazione Istituto Europeo di Oncologia e Centro Cardiologico Monzino

• cardiometabolic dysfunction
• growth hormone-releasing hormone agonist
• heart failure
• preserved ejection fraction

• Animals
• Mice
• Cardiomegaly
• Disease Models, Animal
• Fibrosis
• Growth Hormone-Releasing Hormone
• Heart Failure
• Inflammation
• NG-Nitroarginine Methyl Ester
• Stroke Volume/physiology
• Vascular Endothelial Growth Factor A
• Ventricular Function, Left

• S10 OD023579 NIH HHS
• R01 HL107110 NHLBI NIH HHS
• UM1 HL113460 NHLBI NIH HHS
• R01 CA136387 NCI NIH HHS
• R01 HL137355 NHLBI NIH HHS
• R01 HL134558 NHLBI NIH HHS
• Lipson Foundation
• U.S. Department of Veterans Affairs
• HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
• Soffer Family Foundation (Soffer Family Foundation Inc)
• Starr Foundation (TSF)
• HHS | NIH | National Cancer Institute (NCI)
• Leonard M. Miller School of Medicine, University of Miami

• Hypoplastic left heart syndrome
• Lomecel-B
• allogeneic medicinal signalling cells
• mesenchymal stem cells
• mesenchymal stromal cells

• R01 HL145644 NHLBI NIH HHS
• Maryland Stem Cell Research Fund
• Children’s Heart Foundation
• National Institutes of Health
• National Heart, Lung, and Blood Institute
• Moseley Foundation
• NIH
• National Cancer Institute
• Soffer Family Foundation
• Marcus Foundation
• Starr Foundation
• National Institute on Aging, the MSCRF, and Alzheimer’s Association

• COVID
• MSC
• cytokine storm
• hospital recovery
• pulmonary

• Aged
• COVID-19/therapy
• Cell- and Tissue-Based Therapy
• Female
• Humans
• Male
• Respiratory Distress Syndrome/therapy

Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to future health complications including type-2 diabetes mellitus, hypertension, and cardiovascular disease. A key mechanism by which these complications occur is through stress-induced dysfunction of endothelial progenitor cells (EPCs), including endothelial colony-forming cells (ECFCs). Although several approaches have been previously explored to restore endothelial function, their widespread adoption remains tampered by systemic side effects of adjuvant drugs and unintended immune response of gene therapies. Here, we report a strategy to rejuvenate circulating vascular progenitor cells by conjugation of drug-loaded liposomal nanoparticles directly to the surface of GDM-exposed ECFCs (GDM-ECFCs). Bioactive nanoparticles can be robustly conjugated to the surface of ECFCs without altering cell viability and key progenitor phenotypes. Moreover, controlled delivery of therapeutic drugs to GDM-ECFCs is able to normalize transgelin (TAGLN) expression and improve cell migration, which is a critical key step in establishing functional vascular networks. More importantly, sustained pseudo-autocrine stimulation with bioactive nanoparticles is able to improve in vitro and in vivo vasculogenesis of GDM-ECFCs. Collectively, these findings highlight a simple, yet promising strategy to rejuvenate GDM-ECFCs and improve their therapeutic potential. Promising results from this study warrant future investigations on the prospect of the proposed strategy to improve dysfunctional vascular progenitor cells in the context of other chronic diseases, which has broad implications for addressing various cardiovascular complications, as well as advancing tissue repair and regenerative medicine.

Drug-loaded liposomal nanoparticles conjugated to endothelial colony-forming cells can improve the vasculogenic potential of vascular progenitor cells exposed to gestational diabetes mellitus.

Ischemic heart disease (IHD) is the leading cause of morbidity and mortality worldwide. Ischemia and hypoxia following myocardial infarction (MI) cause subsequent cardiomyocyte (CM) loss, cardiac remodeling, and heart failure. Endothelial progenitor cells (EPCs) are involved in vasculogenesis, angiogenesis and paracrine effects and thus have important clinical value in alternative processes for repairing damaged hearts. In fact, this study showed that the endogenous repair of EPCs may not be limited to a single cell type. EPC interactions with cardiac cell populations and mesenchymal stem cells (MSCs) in ischemic heart disease can attenuate cardiac inflammation and oxidative stress in a microenvironment, regulate cell survival and apoptosis, nourish CMs, enhance mature neovascularization, alleviate adverse ventricular remodeling after infarction and enhance ventricular function. In this review, we introduce the definition and discuss the origin and biological characteristics of EPCs and summarize the mechanisms of EPC recruitment in ischemic heart disease. We focus on the crosstalk between EPCs and endothelial cells (ECs), smooth muscle cells (SMCs), CMs, cardiac fibroblasts (CFs), cardiac progenitor cells (CPCs), and MSCs during cardiac remodeling and repair. Finally, we discuss the translation of EPC therapy to the clinic and treatment strategies.

• heart regeneration
• human blood pressure
• mesenchymal stem cells

• Endothelium
• Endothelium, Vascular
• Humans
• Predictive Value of Tests
• Regeneration

Advanced therapy medicinal products (ATMPs) are medicines for human use based on genes, cells or tissue engineering. After clear successes in adults, the nascent technology now sees increasing pediatric application. For many still untreatable disorders with pre- or perinatal onset, timely intervention is simply indispensable; thus, prenatal and pediatric applications of ATMPs hold great promise for curative treatments. Moreover, for most inherited disorders, early ATMP application may substantially improve efficiency, economy and accessibility compared with application in adults. Vindicating this notion, initial data for cell-based ATMPs show better cell yields, success rates and corrections of disease parameters for younger patients, in addition to reduced overall cell and vector requirements, illustrating that early application may resolve key obstacles to the widespread application of ATMPs for inherited disorders. Here, we provide a selective review of the latest ATMP developments for prenatal, perinatal and pediatric use, with special emphasis on its comparison with ATMPs for adults. Taken together, we provide a perspective on the enormous potential and key framework parameters of clinical prenatal and pediatric ATMP application.

Indices of cardiovascular disease (CVD) risk, vascular endothelial dilation, arterial stiffness and endothelial repair were examined in persons with HIV (PWH) on an antiretroviral therapy (ART) that included abacavir (ABC+) in comparison with PWH on ART without abacavir (ABC-), and with HIV seronegative (HIV-) individuals.

The 115 participants (63% men), aged 30–50 years, did not have CVD, metabolic, endocrine, or chronic renal conditions. PWH were on stable ART for six-months or more. Vascular assessments included flow-mediated dilation (FMD), aortic, radial and femoral arterial stiffness (cAIx, crPWV, cfPWV), and thigh and calf arterial compliance (Vmax50). Endothelial repair was indexed by endothelial progenitor cell colony forming units (EPC-CFU). Traditional CVD risk measures included blood pressure, central adiposity, lipids, insulin resistance (HOMA-IR), CRP and ASCVD score. Analyses controlled for demographics (age, sex, education), medications (antihypertensive, statin/fibrate, antipsychotic), and substance abuse (ASSIST).

No group differences were observed in central adiposity, HOMA-IR, CRP, or ASCVD risk score. However, the ABC- group displayed greater dyslipidemia. The ABC+ group displayed no difference on FMD, cAIx, cfPWV or calf Vmax50 compared with other groups. When CD4 count and viral load were controlled, no additional differences between the ABC+ and ABC- groups emerged. Analyses of crPWV and thigh Vmax50 suggested supported by a trend toward lower EPC-CFU in the HIV+ groups than the HIV- group.

Findings indicate that ABC treatment of 30–50 year-old PWH on stable ART is not likely to contribute in a robust way to higher CVD risk.

• Adult
• Anti-HIV Agents/adverse effects
• CD4 Lymphocyte Count
• Dideoxynucleosides/therapeutic use
• Female
• HIV Infections/complications
• HIV Infections/drug therapy
• Humans
• Male
• Middle Aged
• Vascular Diseases/drug therapy

• Gilead Sciences
• Miami Center for AIDS Research

Left ventricular hypertrophy and heart failure with preserved ejection fraction (HFpEF) are primary manifestations of the cardiorenal syndrome in patients with chronic kidney disease (CKD). Therapies that improve morbidity and mortality in HFpEF are lacking. Cell-based therapies promote cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that cell-based therapy ameliorates CKD-induced HFpEF.

Yorkshire pigs (n = 26) underwent 5/6 embolization-mediated nephrectomy. CKD was confirmed by increased creatinine and decreased glomerular filtration rate (GFR). Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks. HFpEF was evident at 4 weeks by increased LV mass, relative wall thickening, end-diastolic pressure, and end-diastolic pressure-volume relationship, with no change in ejection fraction (EF). Four weeks post-embolization, allogeneic (allo) bone marrow-derived mesenchymal stem cells (MSC; 1 × 10⁷ cells), allo-kidney-derived stem cells (KSC; 1 × 10⁷ cells), allo-cell combination therapy (ACCT; MSC + KSC; 1:1 ratio; total = 1 × 10⁷ cells), or placebo (Plasma-Lyte) was delivered via intra-renal artery. Eight weeks post-treatment, there was a significant increase in MAP in the placebo group (21.89 ± 6.05 mmHg) compared to the ACCT group. GFR significantly improved in the ACCT group. EF, relative wall thickness, and LV mass did not differ between groups at 12 weeks. EDPVR improved in the ACCT group, indicating decreased ventricular stiffness.

Intra-renal artery allogeneic cell therapy was safe in a CKD swine model manifesting the characteristics of HFpEF. The beneficial effect on renal function and ventricular compliance in the ACCT group supports further research of cell therapy for cardiorenal syndrome.

• Allogeneic Cells
• Animals
• Cardio-Renal Syndrome/therapy
• Chronic Disease
• Heart Failure/therapy
• Humans
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic/complications
• Renal Insufficiency, Chronic/therapy
• Stroke Volume
• Swine

• R01 HL107110 NIH HHS
• NHLBI-ECB-HB-2016-09-JB NHLBI NIH HHS
• R01 HL134558 NHLBI NIH HHS
• UM1 HL113460 NHLBI NIH HHS
• R01 HL137355 NHLBI NIH HHS
• UM1 HL087318 NHLBI NIH HHS
• National Institutes of Health
• National Heart, Lung, and Blood Institute

• Hematopoietic Stem Cell Transplantation
• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells
• Transplantation, Autologous

• Acute respiratory distress syndrome
• Anti-inflammatory
• COVID-19
• Cardiovascular diseases
• Inflammation
• Mesenchymal stem cells
• Pneumonia
• Pulmonary fibrosis
• Regeneration
• Renal injury
• SARS-CoV-2

• Blavatnik Biomedical Accelerator at Harvard University

• Arrhythmias, Cardiac/epidemiology
• Bias
• Cardiomyopathy, Dilated/mortality
• Cardiomyopathy, Dilated/therapy
• Cause of Death
• Granulocyte Colony-Stimulating Factor/therapeutic use
• Humans
• Placebos/therapeutic use
• Quality of Life
• Randomized Controlled Trials as Topic
• Severity of Illness Index
• Stem Cell Transplantation/adverse effects
• Stem Cell Transplantation/mortality
• Walk Test
• Watchful Waiting

While existing remedies failed to fully address the consequences of heart failure, stem cell therapy has been introduced as a promising approach. The present review is a comprehensive appraisal of the impacts of using mesenchymal stem cells (MSCs) in clinical trials mainly conducted on ischemic cardiomyopathy. The benefits of MSC therapy for dysfunctional myocardium are likely attributed to numerous secreted paracrine factors and immunomodulatory effects. The positive outcomes associated with MSC therapy are scar size reduction, reverse remodeling, and angiogenesis. Also, a decreasing in the level of chronic inflammatory markers of heart failure progression like TNF-α is observed. The intense inflammatory reaction in the injured myocardial micro-environment predicts a poor response of scar tissue to MSC therapy. Subsequently, the interval delay between myocardial injury and MSC therapy is not yet determined. The optimal requested dose of cells ranges between 100 to 150 million cells. Allogenic MSCs have different advantages compared to autogenic cells and intra-myocardial injection is the preferred delivery route. The safety and efficacy of MSCs-based therapy have been confirmed in numerous studies, however several undefined parameters like route of administration, optimal timing, source of stem cells, and necessary dose are limiting the routine use of MSCs therapeutic approach in clinical practice. Lastly, pre-conditioning of MSCs and using of exosomes mediated MSCs or genetically modified MSCs may improve the overall therapeutic effect. Future prospective studies establishing a constant procedure for MSCs transplantation are required in order to apply MSC therapy in our daily clinical practice and subsequently improving the overall prognosis of ischemic heart failure patients.

• Clinical trials
• Ischemic cardiomyopathy
• Mesenchymal stem cells

The U.S. Food and Drug Administration (FDA) provides guidance for expanded access to experimental therapies, which in turn plays an important role in the Twenty-first Century Cures Act mandate to advance cell-based therapy. In cases of incurable diseases where there is a lack of alternative treatment options, many patients seek access to cell-based therapies for the possibility of treatment responses demonstrated in clinical trials. Here, we describe the use of the FDA’s expanded access to investigational new drug (IND) to address rare and emergency conditions that include stiff-person syndrome, spinal cord injury, traumatic brain stem injury, complex congenital heart disease, ischemic stroke, and peripheral nerve injury. We have administered both allogeneic bone marrow-derived mesenchymal stem cell (MSC) and autologous Schwann cell (SC) therapy to patients upon emergency request using Single Patient Expanded Access (SPEA) INDs approved by the FDA. In this report, we present our experience with 10 completed SPEA protocols.

• clinical investigation
• expanded access IND
• mesenchymal stem cells
• schwann cell
• single patient IND

Mesenchymal stromal cells (MSCs) are under active consideration as a treatment strategy for controlling the hyper-inflammation and slow disease progression associated with coronavirus disease 2019 (COVID-19). The possible mechanism of protection through their immunoregulatory and paracrine action has been reviewed extensively. However, the importance of process control in achieving consistent cell quality, maximum safety and efficacy—for which the three key questions are which, when and how much—remains unaddressed. Any commonality, if it exists, in ongoing clinical trials has yet to be analyzed and reviewed. In this review, the authors have therefore compiled study design data from ongoing clinical trials to address the key questions of “which” with regard to tissue source, donor profile, isolation technique, culture conditions, long-term culture and cryopreservation of MSCs; “when” with regard to defining the transplantation window by identifying and staging patients based on their pro-inflammatory profile; and “how much” with regard to the number of cells in a single administration, number of doses and route of transplantation. To homogenize MSC therapy for COVID-19 on a global scale and to make it readily available in large numbers, a shared understanding and uniform agreement with respect to these fundamental issues are essential.

• CD142
• MSC dosage
• SARS-CoV-2
• cytokine storm
• hyper-coagulopathy
• immunomodulation

• Cardiac inducers
• Cardiomyocytes
• Exosomes
• Growth factors
• Mesenchymal stem cells
• Microenvironment
• micro RNA

• angiogenesis
• arthritis
• autoimmune disease
• mesenchymal stem cells (MSCs)
• tube formation

• ABCB5
• GMP manufacturing
• advanced therapy medicinal product
• chronic wound
• mesenchymal stromal cells
• venous ulcer

• ATP Binding Cassette Transporter, Subfamily B
• Humans
• Immunomodulation
• Manufacturing Industry
• Mesenchymal Stem Cells
• Quality Control
• Skin

• I01 BX000516 BLRD VA
• R24 EY028767 NEI NIH HHS
• P01 AG071463 NIA NIH HHS
• R01 EY025794 NEI NIH HHS
• I01 RX000989 RRD VA

Endothelial progenitor cells (EPCs) improve endothelial impairment, which in turn restores endothelial function in patients with heart failure (HF). In the present study, we tested whether fenofibrate, with its anti-inflammatory and vasoprotective effects, could improve myocardial function by activating EPCs through the eNOS pathway in a doxorubicin (DOX)-induced cardiomyopathy mouse model. Wild-type mice were divided into 4 groups and treated with vehicle, DOX + saline, DOX + fenofibrate, and DOX + fenofibrate + L-NAME (N(ω)-nitro-L-arginine methyl ester). DOX-induced cardiac atrophy, myocardial dysfunction, the number of circulating EPCs and tissue inflammation were analyzed. Mice in the DOX + fenofibrate group had more circulating EPCs than those in the DOX + saline group (2% versus 0.5% of total events, respectively) after 4 weeks of treatment with fenofibrate. In addition, the inhibition of eNOS by L-NAME in vivo further abolished the fenofibrate-induced suppression of DOX-induced cardiotoxic effects. Protein assays revealed that, after DOX treatment, the differential expression of MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metalloproteinase-9), TNF-α (tumor necrosis factor-α), and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) between saline- and DOX-treated mice was involved in the progression of HF. Mechanistically, fenofibrate promotes Akt/eNOS and VEGF (vascular endothelial growth factor), which results in the activation of EPC pathways, thereby ameliorating DOX-induced cardiac toxicity.

• Frailty
• cognitive frailty
• mesenchymal stem cell therapy

• Aged
• Cognition
• Frail Elderly
• Frailty/therapy
• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells

Arteriosclerosis is an age-related disease and a leading cause of cardiovascular disease. In animal experiments, mesenchymal stem cells and its culture-conditioned medium have been shown to be promising tools for prevention or treatment of arteriosclerosis. On the basis of these evidences, we aimed to assess whether administration of autologous adipose-derived mesenchymal stem cells (Ad-MSC) is safe and effective for treatment of arteriosclerosis.

We retrospectively reviewed clinical records of patients with arteriosclerosis who had received autologous Ad-MSC administration at our clinic. Patients’ characteristics were recorded and data on lipid profile, intimal-media thickness (IMT), cardio-ankle vascular index (CAVI), and ankle-brachial index (ABI) before and after Ad-MSC administration were collected and compared.

Treatment with Ad-MSC significantly improved HDL, LDL, and remnant-like particle (RLP) cholesterol levels. No adverse effect or toxicity was observed in relation to the treatment. Of the patients with abnormal HDL values before treatment, the vast majority showed improvement in the values. Overall, the measurements after treatment were significantly increased compared with those before treatment (p < 0.01). In addition, decreases in LDL cholesterol and RLP levels were observed after treatment in patients who had abnormal LDL cholesterol or RLP levels before treatment. The majority of patients with pre-treatment abnormal CAVI values had improved values after treatment. In patients with available IMT values, a significant decrease in the IMT values was found after therapy (p < 0.01). All patients with borderline arteriosclerosis disease had improved laboratory findings after treatment. In general, post-treatment values were significantly decreased as compared with pre-treatment values. Of the patients with normal ABI values before treatment at the same time as CAVI, the vast majority remained normal after treatment.

These findings suggest that Ad-MSC administration is safe and effective in patients developing arteriosclerosis, thereby providing an attractive tool for anti-aging application.

• Adipose-derived mesenchymal stem cell
• Anti-aging
• Arteriosclerosis
• Efficacy
• Safety

• COVID-19
• cardiovascular
• cytokine storm
• mesenchymal stem cells
• regeneration and repair

Non-ischemic dilated cardiomyopathy (NIDCM) constitutes one of the most common causes to non-ischemic heart failure. Despite treatment, the disease often progresses, causing severe morbidity and mortality, making novel treatment strategies necessary. Due to the regenerative actions of mesenchymal stem cells (MSCs), they have been proposed as a treatment for NIDCM. This systematic review aims to evaluate efficacy and mode of action (MoA) of MSC-based therapies in NIDCM. A systematic literature search was conducted in Medline (Pubmed) and Embase. A total of 27 studies were included (3 clinical trials and 24 preclinical studies). MSCs from different tissues and routes of delivery were reported, with bone marrow-derived MSCs and direct intramyocardial injections being the most frequent. All included clinical trials and 22 preclinical trials reported an improvement in cardiac function following MSC treatment. Furthermore, preclinical studies demonstrated alterations in tissue structure, gene, and protein expression patterns, primarily related to fibrosis and angiogenesis. Consequently, MSC treatment can improve cardiac function in NIDCM patients. The MoA underlying this effect involves anti-fibrosis, angiogenesis, immunomodulation, and anti-apoptosis, though these processes seem to be interdependent. These encouraging results calls for larger confirmatory clinical studies, as well as preclinical studies utilizing unbiased investigation of the potential MoA.

• dilated cardiomyopathy
• mesenchymal stem cells
• mode of action
• regeneration