Derived Stem Cell Transplantation Research Articles

BONE MARROW-DERIVED STEM CELL TRANSPLANTATION FOR OSTEOCHONDRAL DEFECTS OF THE KNEE: A PROSPECTIVE CLINICAL STUDY

AbstractBackgroundAutologous chondrocyte implantation is a NICE approved intervention however it involves the morbidity of two operations, a prolonged rehabilitation and substantial healthcare costs. This study describes a novel, one-step, bone marrow (BM) derived mesenchymal stem cell (MSC) transplantation technique for treating knee osteochondral lesions and presents our prospective clinical study investigating the success of this technique in 206 lesions over a 5 year period.MethodologyThe surgical technique involves harvesting BM from patients’ anterior superior iliac spines, centrifugation to isolate MSCs and seeding into a type 1 collagen scaffold (SyngenitTM Biomatrix). Autologous fibrin glue is used to secure the scaffold into the defect. Inclusion criteria included patients aged 15 – 55 years old with symptomatic osteochondral lesions >1cm2. Exclusion criteria included patients with ligament instability, uncorrected alignment, inflammatory arthropathy and a Body Mass Index >35 kg/m2. Outcome measures included the Modified Cincinnati Knee Rating System (MCKRS), complications and reoperations.ResultsMean MCKR scores showed statistically significant improvements compared to pre-operative scores at 6 months 58.79 ± 3.5 and 1 year postoperatively 63.82 ± 3.93 with further improvements at 2 years and 5 years which did not reach statistical significance. Survival rates were 97.9%, 94% and 93.2% at 1, 2 and 5 years. Multiple regression analysis identified previous cartilage surgery, microfracture and age as factors affecting MCKRS scores (p < 0.029, 0.001 and 0.030, respectively).ConclusionsOne-step BM derived stem cell transplantation demonstrates satisfactory outcomes over a 5 year period.

Repigmentation by combined narrow‑band ultraviolet B/adipose‑derived stem cell transplantation in the mouse model: Role of Nrf2/HO‑1‑mediated Ca2+ homeostasis.

Vitiligo is a depigmentation disease commonly seen in clinical practice, mainly involving loss of functional epidermal pigment cells and hair follicle melanocytes. Narrow-band ultraviolet B (NB-UVB) has emerged as the first choice of treatment for vitiligo, but long-term exposure may have serious consequences. Recently, it was reported that adipose-derived stem cells (ADSCs) improve melanocyte growth and the efficacy of melanocyte transplantation. The present study aimed to examine the efficacy of NB-UVB/ADSC-transplantation combined therapy on a mouse vitiligo model and explore the underlying mechanisms by focusing on endoplasmic reticulum stress and cellular calcium (Ca2+) homeostasis. Vitiligo mice models were established by applying 40% monobenzone (MBZ) cream twice daily and treated with NB-UVB/ADSC combination therapy. Some treated mice were also given ML385, a nuclear factor erythroid 2 like 2 (Nr2) inhibitor. Histopathological changes were evaluated using a depigmentation evaluation score and observed with hematoxylin and eosin staining on skin tissues. ELISA was used to measure diagnostic markers in plasma. Flow cytometric assay was performed to quantify CD3+, CD4+ and CD8+ levels. Expression levels of associated proteins were detected with western blot and immunofluorescence. Treatment of mice with MBZ-induced depigmentation patches on the skin was accompanied with loss of redox balance and disruption of cellular Ca2+ homeostasis. Oxidative stress and Ca2+ unbalancing were improved after the mice were treated by NB-UVB/ADSCs transplantation combination therapy. ML385, strongly negated the protective effect of NB-UVB/ADSC transplantation combination therapy, indicating the critical role of Nr2 signaling. The findings improved the understanding of the pathogenesis of vitiligo and will guide future development of therapeutic strategies against it.

Host pre-conditioning improves human adipose-derived stem cell transplantation in ageing rats after myocardial infarction: Role of NLRP3 inflammasome.

Functional decline of stem cell transplantation in ageing hosts is well documented. The mechanism for this is poorly understood, although it is known that advancing age does not provide an optimal milieu for exogenous stem cells to survive, engraft and differentiate. We showed that n‐butylidenephthalide improved human adipose–derived stem cell (hADSC) engraftment via attenuating the production of reactive oxygen species (ROS). It remained unclear whether pre‐treated hosts with n‐butylidenephthalide can rejuvenate the ageing heart and improve hADSC engraftment by regulating the ROS/NLRP3 inflammasome‐mediated cardiac fibrosis after myocardial infarction. One hour after coronary ligation, hADSCs were transplanted into the hearts of young and ageing Wistar rats that were pre‐treated with or without n‐butylidenephthalide for 3 days. At day 3 after infarction, myocardial infarction was associated with an increase in ROS levels and NLRP3 inflammasome activity with age. hADSC transplant effectively provided a significant decrease in ROS levels, NLRP3 inflammasome activity, IL‐1β levels and cardiac fibrosis in either young or old infarcted rats. However, the beneficial effects of hADSCs were greater in young compared with old rats in terms of NLRP3 inflammasome activity. The infarcted ageing rats pre‐conditioned by n‐butylidenephthalide improved engraftment and differentiation of hADSCs and additionally attenuated cardiac fibrosis compared with hADSCs alone. The anti‐inflammation effects of n‐butylidenephthalide were reversed by SIN‐1. In conclusions, the increased NLRP3 inflammasome activity plays the pathogenesis of ageing‐related functional hADSC decline in the ageing hosts. n‐butylidenephthalide‐pre‐treated ageing hosts reversibly ameliorate the harsh microenvironments, improve stem cell engraftment and attenuate cardiac fibrosis after myocardial infarction.

Comparison of Umbilical Cord Blood Transplantation with Bone Marrow or Peripheral Blood Derived Stem-Cell Transplantation in Transfusion Dependent Thalassemia Patients: A Single Center Propensity Score Matching Analysis

Comparison of Umbilical Cord Blood Transplantation with Bone Marrow or Peripheral Blood Derived Stem-Cell Transplantation in Transfusion Dependent Thalassemia Patients: A Single Center Propensity Score Matching Analysis

Bone Marrow-Derived Stem Cells as a Cytotherapy for Sirolimus-Induced Periodontal Ligament and Alveolar Bone Injury in a Rat Model

Background: Sirolimus is known to be the most common immunosuppressive and anti-cancer drug regardless to its adverse side effects. Bone marrow derived -mesenchymal cells represent a great interest, particularly in the areas of regenerative medicine. Aim of the study: The current research aimed to examine the efficacy of stem cell transplantation for treating the periodontal ligament and alveolar bone affection that caused by Sirolimus.Materials and methods: Fifty male albino rats with average body weight 200-250 gram were used in this investigation. The animals were divided into the following groups: Group I: 20 rats served as controls and subdivided into 2 subgroups 10 animals each: Group I.1: Using a curved metallic oral gavage, ethanol and saline were given in a daily oral dose of 10 mg/kg body weight to Group I.1 for 3 months. Group I.2: treated with the same way as group I.1 then left untreated for 2 weeks Group II: 20 animals subdivided into 2 subgroups, 10 animals each: Group II.1 (Sirolimus group) treated with immunosuppressive drug (Rapamycin) dissolved in ethanol and saline in a daily oral dose of 10 mg/kg body weight using a curved metallic oral gavage for 3 months. Group II.2: (Recovery group) treated with the same dose and route of administration of group II.1 for 3 months then left untreated for 2 weeks as a recovery period. Group III: 10 rats treated with the same dose of Rapamycin in group II then injected by a single intravenous infusion of mesenchymal bone marrow stem cells. For bone marrow- mesenchymal cells isolation and culture, ten adult male albino rats were used as a source of bone marrow. At the end of experiment, the rats were sacrificed, the jaws of rats were dissected out and processed to be stained with: Hematoxylin and eosin staining for histological examination. Streptavidin-biotin immunohistochemical method for Vimentin and CD44 localization for stem cells characterization and homing detection respectively and streptavidin-biotin immunohistochemical method of Bcl2 for anti-apoptotic expression detection. Results: Sirolimus showed dramatic degenerative changes on the periodontal ligaments and alveolar bone, however the transplanted stem cell helped tissues to partially retain their texture and accelerate their healing. Conclusion Sirolimus caused severe adverse effects on the periodontal ligaments and alveolar bone which did not resolved after recovery period of 2 weeks, however, the degeneration was more dramatic. Interestingly, bone marrow- derived stem cells transplantation represented a promising attempt to overcome the Sirolimus drawbacks.

Reduction of Inflammation and Enhancement of Motility after Pancreatic Islet Derived Stem Cell Transplantation Following Spinal Cord Injury.

ObjectiveSpinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. MethodsrPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, S100β, brain derived neurotrophic factor (BDNF), 2’,3’-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor [TGF]-β, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. ResultsrPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), β3-tubulin and nestin as well as antiinflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. ConclusionTransplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

Effects of low-intensity electrical stimulation and adipose derived stem cells transplantation on the time-domain analysis-based electromyographic signals in dogs with SCI

IntroductionThe application of low-intensity electrical stimulation (LIES) to neural tissue increases neurochemical factors responsible for regeneration as nerve growth factor. Stem cell (SC) therapy for patients with Spinal cord injury (SCI) promote some increase functional improvement. ObjectiveInvestigate the electromyographic response in paraplegic dogs undergoing LIES and SC transplantation. Methods27 dogs paraplegics with SCI were divided into three groups with different types of therapy. GADSC: two SC transplants (n = 9); GLIES: LIES (n = 8); GCOMB: two SC transplants and LIES (n = 10). Adipose derived mesenchymal stem cells (ADSCs) were transplanted by lumbar puncture in the amount of 1.2 × 106 cells/50 μL. Acupuncture needles positioned in the interspinous space were used for stimulation. The electrical stimulation was applied with a mean voltage ∼30 mV and four consecutive modulated frequencies (5 Hz, 10 Hz, 15 Hz and 20 Hz) within 5 min each. The patients motor performance was evaluated before (Pre) the procedure and after 30 (Post30) and 60 (Post60) days, from electromyography root mean square (EMGRMS) registered with subcutaneous electrodes in the vastus lateralis muscle, while the animals were in quadrupedal position. ResultsAll three groups showed a significant intra-group increase of EMGRMS (Pre vs. Post30 or Pre vs. Post60). However, there were no statistically significant differences between Post30 and Post60. The inter-group test (GADSC X GLIES X GCOMB) did not present significance when compared the instants Pre (p = 0.34), Post30 (p = 0.78) and Post60 (p = 0.64). ConclusionSome dogs recovered motor activity, expressed by the EMGRMS, in all groups, in pre vs. post (30 or 60 days) comparisons.

Allogenic Adipose Derived Stem Cells Transplantation Improved Sciatic Nerve Regeneration in Rats: Autologous Nerve Graft Model.

We examined the effect of transplantation of allogenic adipose-derived stem cells (ADSCs) with properties of mesenchymal stem cells (MSCs) on posttraumatic sciatic nerve regeneration in rats. We suggested an approach to rat sciatic nerve reconstruction using the nerve from the other leg as a graft. The comparison was that of a critical 10 mm nerve defect repaired by means of autologous nerve grafting versus an identical lesion on the contralateral side. In this experimental model, the same animal acts simultaneously as a test model, and control. Regeneration of the left nerve was enhanced by the use of ADSCs, whereas the right nerve healed under natural conditions. Thus the effects of individual differences were excluded and a result closer to clinical practice obtained. We observed significant destructive changes in the sciatic nerve tissue after surgery which resulted in the formation of combined contractures in knee and ankle joints of both limbs and neurotrophic ulcers only on the right limb. The stimulation of regeneration by ADSCs increased the survival of spinal L5 ganglia neurons by 26.4%, improved sciatic nerve vascularization by 35.68% and increased the number of myelin fibers in the distal nerve by 41.87%. Moreover, we have demonstrated that S100, PMP2, and PMP22 gene expression levels are suppressed in response to trauma as compared to intact animals. We have shown that ADSC-based therapy contributes to significant improvement in the regeneration.

Murine Hair Follicle Derived Stem Cell Transplantation onto the Cornea Using a Fibrin Carrier.

The goal of this protocol is to establish a procedure for cultivating stem cells on a fibrin carrier to allow for eventual transplantation to the eye. The ability to transfer stem cells to a patient is critical for treatment for a variety of disorders and wound repair. We took hair follicle stem cells from the vibrissae of transgenic mice expressing a dual reporter gene under the control of the Tet-on system and the keratin 12 promoter (Meyer- Blazejewska et al., 2011 ). A clonal growth assay was performed to enrich for stem cells. Once holoclones formed they were transferred onto a fibrin carrier and cultivated to obtain a confluent epithelial cell layer. Limbal stem cell deficient (LSCD) mice were used as the transplant recipient in order to test for successful grafting and eventual differentiation into a corneal epithelial phenotype.

Bone marrow derived mesenchymal stem cell transplantation for treatment of denervated intrinsic paw muscular atrophy: an experimental research in rats

Objective To investigate the feasibility of bone marrow derived mesenchymal stem cell (BMSC) transplantation in the treatment of denervated intrinsic paw muscle atrophy. Methods Twelve adult male Sprague-Dawley rats (24 sides) were randomly divided into ulnar nerve transection group, stem cell transplantation group, culture medium injection group and normal control group. GFP-transfected BMSCs cultured in vitro were injected into the paw muscles of rats in the stem cell transplantation group. After 1 month, intrinsic paw muscles were tested by histology, immunofluorescence and PCR. Results The muscle wet weight and muscle fiber cross-sectional area of stem cell transplantation group were 66% and 63% of normal control group, respectively, and twice as much as that of ulnar nerve transection and culture medium injection groups (P<0.05). GFP-positive mesenchymal stem cells still could be detected at injection site. The expression of VEGF, HGF, CNTF, bFGF in stem cell transplantation group were higher than that in ulnar nerve transection and culture medium injection groups, and the apoptotic index (apoptotic cells/total cells) in stem cell transplantation group was smaller (P<0.05). Conclusion BMSCs can effectively delay the denervated intrinsic paw muscular atrophy. BMSCs may have the capbility of secreting neurotrophic factor and reducing muscle tissue apoptosis. Key words: Mesenchymal stem cell transplantation; Muscular atrophy; Intrinsic paw muscles; Animal experimentation

CORRECTION: Adipose derived stem cell transplantation is better than bone marrow mesenchymal stem cell transplantation in treating hindlimb ischemia in mice

The Figure 5 of the article “Adipose derived stem cell transplantation is better than bone marrow mesenchymal stem cell transplantation in treating hindlimb ischemia in mice” that published in 29 Sept 2016, at Vol 3, Issue 9, from page 844-856 (DOI: 10.7603/s40730-016-0046-0) as below&#x0D; &#x0D; that lacked the legend for the violet line should be corrected as:&#x0D; &#x0D; The violet line demonstrated “BM-MSC”.&#x0D; &#x0D; &#x0D;

Rationale for stem cell therapy for type 2 diabetes mellitus

Stem cells can be differentiated into many types of mature cells. Among degenerative diseases, type 1 diabetes mellitus (T1DM) is considered to be a good target disease for stem cell therapeutic application. Indeed, several studies have suggested that stem cells can be differentiated, both in vitro and in vivo, into beta cells which regenerate the pancreas. However, recent studies have shown that stem cell therapy can also provide benefits for type 2 diabetes mellitus (T2DM), which is not related to beta cell degeneration in the pancreas. This commentary will discuss the opportunity to use mesenchymal stem cells (MSCs) to treat T2DM, citing various stem cell therapies from recent published studies. Indeed, a current report “Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus, Biomedical Research and Therapy, 3(12): 1034-1044” evaluated and confirmed the positive effects of stem cell transplantation for blood glucose regulation in T2DM.

Adipose derived stem cells transplantation negative effects (review)

Adipose derived stem cells transplantation negative effects (review)

Adipose derived stem cell transplantation is better than bone marrow mesenchymal stem cell transplantation in treating hindlimb ischemia in mice

Introduction: Bone marrow derived MSCs (BM-MSCs) and adipose derived MSCs (AD-MSCs) are among the types of stem cells most commonly studied. Our study aims to compare the therapeutic efficacy of allograft AD-MSCs versus BM-MSCs in a mouse model of hindlimb ischemia. Methods: AD-MSCs were isolated from belly fat and BM-MSCs were isolated from femur bone marrow. They were used to treat mice with acute hindlimb ischemia. Treatment efficacy was compared among 4 groups: injected with BM-MSCs, injected with AD-MSCs, non-treated and injected with phosphate buffered saline. Mice in the groups were evaluated for the following: necrosis grade of leg, leg edema, blood flow, muscle cell restructure and new blood vessel formation. Results: Results showed that AD-MSC transplantation significantly recovered acute limb ischemia, with 76.5% of mice fully recovered, while the ratio was only 48.5% in BM-MSC transplanted group, and 0% in the non-treated and PBS groups. Evaluation of leg edema, blood flow, muscle cell restructure and new blood vessel formation also supported the observation that AD-MSC transplantation was superior over BM-MSC transplantation. Conclusion: Therefore, AD-MSCs may serve as the more suitable MSC for hindlimb ischemia treatment and angiogenesis therapy.

19 - A Controlled Clinical Trial of Adipose Derived Stem Cell Transplantation for Osteoarthritis

19 - A Controlled Clinical Trial of Adipose Derived Stem Cell Transplantation for Osteoarthritis

Impact of ABO-Mismatch on Treatment Outcome and Transfusional Needs in Non-Myeloablative, Allogeneic, Peripheral Blood Stem Cell Transplantations

Background: Suitable stem cell donors are selected by HLA-typing, CMV status, gender and age. The ABO blood groups are not part of the initial search and selection process. Since ABO-antigens are inherited independently from HLA antigens, patient-donor mismatches may occur and are considered acceptable. However, with the increased use of unrelated donors, more ABO-mismatched transplants are expected to take place. The influence of ABO-mismatched transplants on clinical outcomes has been studied earlier, but is still under debate. Comparisons between studies are challenging because of the heterogeneity of patient populations, conditioning regimes, various stem cell sources and different outcome parameters. Only a few studies have evaluated transfusional needs after ABO mismatched stem cell transplantations.Aim: To gain insight in the impact of ABO-(mis) matching on red blood cell (RBC) transfusion dependency in the first 90 days after transplant and on clinical outcome after 1 year follow-up.Study design and methods: All patients treated from 2004 till 2014 with a first, allogeneic, peripheral blood derived stem cell transplantation after a reduced-intensity conditioning regimen, were included for analyses of treatment outcomes and transfusional needs.Results: In the population for treatment outcome analysis (n=233), 124 patients were ABO-identical, 31 were ABO-major mismatched and 68 were ABO-minor mismatched. Ten patients had a bidirectional ABO-mismatch and were excluded from analyses. Multivariate analysis showed no impact of ABO-mismatch on overall survival, acute graft-versus-host disease (GVHD) incidence, non-relapse related mortality (NRM) and GVHD-related mortality. The minor ABO-mismatch group had more relapse related mortality (RRM) after 1 year (26.5%) compared to the ABO-identical (12.1%, P=0.01) and the ABO-major mismatched group (6.4%, P=0.04). The hazard ratio (HR) for RRM in ABO-minor mismatch patients versus ABO-identical patients was 2.41 (95% confidence interval, 1.14 to 5.08, P=0.021). In the population for transfusion analysis (n=204), 111 patients were ABO-identical, 27 were ABO-major mismatched and 57 were ABO-minor mismatched. Nine patients had a bidirectional ABO-mismatch and were excluded from analyses. No influence of ABO-mismatch on transfusional needs was seen in the first 30 days after transplant. 30-60 days after transplant, 14 (52%) major ABO-mismatched patients needed RBC transfusions with an overall mean of 2.19 RBC units compared to 24 (22%) patients with an overall mean of 0.68 in the ABO-identical group (P=0.001) and 16 patients (28%) with an overall mean of 1.04 in the ABO-minor mismatched group (P=0.028). More than five transfusions were given to 15% of the major ABO-mismatch group, compared to only 3% in the ABO-identical group (Relative risk (RR) 5.0, 95% CI 1.2-21.0, P=0.028) and 5% in the minor ABO-mismatch group (RR 2.8, 95% CI 0.7-11.7, P=0.155). 60-90 days after transplant, the ABO-major mismatch group was still significantly more transfusion dependent with 13 patients needing transfusions (48%) and an overall mean of 2.33 RBC units per patient, compared to 23 patients (21%) with a mean of 1.04 units in the ABO-identical group (P=0.002) and 9 patients (16%) with an mean of 0.58 in the ABO-minor mismatch group (P=0.002). In this period,19% of ABO-major mismatch patients received more than 5 transfusions, compared to 6% in the ABO-identical group (RR 2.9, 95% CI 1.0-8.5, P=0.048) and 2% in the ABO-minor mismatch group (RR 10.6, 95% CI 1.3-86.0, P=0.028). Differences in transfusional needs remained significant regardless of pre-transplant hemoglobin levels. Pure red cell aplasia (PRCA), defined as transfusion dependency from day 30 until longer than day 90 after transplant, was seen in 10 patients with an ABO-major mismatch (37%).Conclusion: ABO-major mismatched patients needed significantly more RBC transfusions in the second and third month after transplant. More relapse related mortality was seen in the minor mismatch group. However, this is probably an artefact due to relatively small patient numbers. Other measures for treatment outcome showed no significant differences. Our results confirm that ABO-matching is not mandatory in donor selection for stem cell transplantation. Still, whenever possible ABO major mismatching should be preferably avoided to decrease transfusion burden. DisclosuresNo relevant conflicts of interest to declare.

Evaluation of the Efficacy of Autologous Bone Marrow Stem Cell Transplantation in Type 1 Diabetes Mellitus.

Diabetes mellitus (DM) is characterized by hyperglycaemia that is often associated with long- term complication, including microvascular (retinopathy, nephropathy, and neuropathy) macro vascular damage. The present study was designed to evaluate the possible role of autologous bone marrow stem cell transplantation for cases of type 1 DM, which could differentiate into insulin- producing β cells and its role in modulating the immune response from T helper 1 to T helper 2. This study was conducted on 10 cases of autoimmune type 1 diabetes mellitus, both males and females. They were selected according to inclusion and exclusion criteria. We observed that 70% of studied subjects decreased in their insulin requirements. Fasting and postprandial blood glucose significantly decreased after transplantation, while levels of C- peptide were significantly increased at the end of 9 months of autologous bone marrow- derived stem cell transplantation (SCT). But glycated haemoglobin significantly decreased after transplantation. No side effects were noted in liver and kidney functions. Our observations indicated that SCT is a safe and effective modality of treatment to improve β- cell function in patients with T1DM.

Abstract 253: The Presence of Coronary Artery Disease Influences Number and Function of Stem Cells in the Bone Marrow

Purpose: Despite the observed therapeutic benefits of autologous bone marrow (BM)-derived stem cell transplantation in patients with ischemic heart disease, the efficacy of this approach could be hampered by BM dysfunction. We investigated whether BM cellularity and function is affected by coronary artery disease (CAD). Methods &amp; Results: BM samples were obtained peri-operatively from 26 CAD patients, undergoing coronary artery bypass surgery (LVEF 54±16%), and 6 controls, undergoing mitral valve surgery (LVEF 50±12%; age 59±10yrs). CAD patients were stratified according to their Syntax score (mild ≤15, age 61±10yrs; and moderate CAD &gt;15, age 63±8yrs; stratification based on median score), which is used to assess complexity of coronary lesions. In vitro functional analysis of isolated BM-derived mononuclear cells (BM-MNC) revealed a significant impairment of migratory capacity towards SDF-1α and VEGF in patients with moderate CAD (25.71±7.3%) compared to controls (33.82±8.3%; p=0.042) and patients with mild CAD (34.76±7.8%; p=0.007). Hematopoetic stem cells (HSC, CD45dimCD34+SSClow) were reduced in patients with moderate CAD (8178±5530 HSC/106 BM-MNC; p=0.014) and mild CAD (10655±5489 HSC/106 BM-MNC; p=0.054) compared to controls (16220±6126 HSC/106 BM-MNC). An inverse correlation was found between age and the number of granulocyte-macrophage colony forming units (r= −0.408; p=0.048), burst forming units erythroid (r= −0.458; p=0.028) and HSC (r=-0.356; p=0.046). Furthermore, our data revealed a relation between reduced renal function (CKD-EPI eGFR, 81.2±19 ml/min) and reduced number of HSC (r=0.480; p=0.011) and endothelial progenitor cells (EPC, CD45dimCD34+KDR+; r=0.522; p=0.008). Conclusions: Migratory capacity of BM-MNC and the number of HSC are reduced in patients with CAD, which is more pronounced in more complex CAD. In addition, age and renal function emerge as relevant determinants on BM function and stem cell populations. Therefore, these factors should be taken into account when assessing benefits of autologous stem cell therapy.

TCTAP A-155 Co-injection Basic Fibroblast Growth Factor for Adipose Derived Stem Cells Transplantation: Improved Cardiac Remodelling and Function of Myocardial Infarction

TCTAP A-155 Co-injection Basic Fibroblast Growth Factor for Adipose Derived Stem Cells Transplantation: Improved Cardiac Remodelling and Function of Myocardial Infarction

Efficacy and safety of autologous bone marrow derived hematopoietic stem cell transplantation in patients with type 2 DM: A 15 months follow-up study.

Background:there are dearths of studies describing the effect of autologous bone marrow derived stem cell transplantation (ABMSCT) through targeted approach in Type 2 Diabetes Mellitus. This study reports the efficacy and safety of super-selective injection of ABMSCT in T2DM.Materials and Methods:Ten patients (8 men and 2 women) with T2DM, with duration of disease >5 years and with documented triple drug failure receiving insulin (0.7 U/Kg/day), metformin and pioglitazone underwent super-selective injection of stem cells into superior pancreaticoduodenal artery under fluoroscopic guidance. The primary outcome measure was decrease in insulin requirement by ≥50% (defined as responders), while secondary endpoints were improvement in glucagon stimulated C-peptide levels, changes in weight, HbA1c, lipid profile and quality of life (QOL) at the end of 15 months.Results:Six patients (60%) were ‘responders’ at 15 months of follow-up showing a reduction in mean insulin requirement by 74% as compared to baseline and one patient was off-insulin till the end of the study. Mean HbA1c reduction in ‘responders’ was 1.1% (8.1 ± 0.5% to 7.0 ± 0.6%, P = 0.03), accompanied with a significant improvement in glucagon stimulated C-peptide levels (P = 0.03), Homeostasis Model Assessment -β (P = 0.03) and QOL scores. However, ‘non-responders’ did not show any significant alterations in these parameters. No serious adverse events were noted.Conclusion:Our observations indicate that ABMSCT is effective in management of T2DM and its efficacy is maintained over a period of 15 months without any adverse events. However, more number of patients and longer duration of follow-up are required to substantiate these observations.