Autologous Bone Marrow Stem Cell Research Articles

Zoledronic Acid and Enriched Autologous Bone Marrow Stem Cell Implantation for Femoral Head Osteonecrosis

Zoledronic Acid and Enriched Autologous Bone Marrow Stem Cell Implantation for Femoral Head Osteonecrosis

Epigenetic mechanisms regulate sex differences in cardiac reparative functions of bone marrow progenitor cells

Historically, a lower incidence of cardiovascular diseases (CVD) and related deaths in women as compared with men of the same age has been attributed to female sex hormones, particularly estrogen and its receptors. Autologous bone marrow stem cell (BMSC) clinical trials for cardiac cell therapy overwhelmingly included male patients. However, meta-analysis data from these trials suggest a better functional outcome in postmenopausal women as compared with aged-matched men. Mechanisms governing sex-specific cardiac reparative activity in BMSCs, with and without the influence of sex hormones, remain unexplored. To discover these mechanisms, Male (M), female (F), and ovariectomized female (OVX) mice-derived EPCs were subjected to a series of molecular and epigenetic analyses followed by in vivo functional assessments of cardiac repair. F-EPCs and OVX EPCs show a lower inflammatory profile and promote enhanced cardiac reparative activity after intra-cardiac injections in a male mouse model of myocardial infarction (MI). Epigenetic sequencing revealed a marked difference in the occupancy of the gene repressive H3K9me3 mark, particularly at transcription start sites of key angiogenic and proinflammatory genes in M-EPCs compared with F-EPCs and OVX-EPCs. Our study unveiled that functional sex differences in EPCs are, in part, mediated by differential epigenetic regulation of the proinflammatory and anti-angiogenic gene CCL3, orchestrated by the control of H3K9me3 by histone methyltransferase, G9a/Ehmt2. Our research highlights the importance of considering the sex of donor cells for progenitor-based tissue repair.

Effect of mesenchymal stromal cells transplantation on the outcomes of patients with knee osteoarthritis: A systematic review and meta-analysis.

Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell transplantation from different sources for the treatment of knee osteoarthritis (KOA) remains controversial. This study integrates and evaluates the previously published data of stem cell transplantation for KOA to explore the curative effect of different stem cells. We conducted a meta-analysis of randomized controlled trials on stem cell therapy for KOA. Measures of efficacy included Visual Analog Scale (VAS), Lequesne index, Lysholm Knee Scoring Scale (LKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Joint injury was evaluated through the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. We analyzed 16 studies involving 875 KOA patients. The stem cell treatment showed significant VAS reduction from the third month onwards. Subgroup analysis suggested the most significant pain relief at different postoperative months came from adipose-derived and umbilical cord-derived stem cells. Autologous adipose tissue resulted in better pain alleviation compared with allogenic. However, autologous bone marrow stem cells did not show increased pain relief over allogeneic ones. Combination therapy (HA and/or PRP) showed no effect. Autologous adipose-derived stem cells demonstrate the most effective recovery of knee joint function. In WORMS assessment, there was no significant difference between the stem cell group and control. Stem cell transplantation proved safe and effective for KOA treatment. Different sources stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.

Autologous mesenchymal stem cell therapy for diabetic men with erectile dysfunction. Is it promising? A pilot study.

to assess safety and efficacy of autologous mesenchymal bone marrow stem cell injection in penile cavernosal tissue for erectile dysfunction therapy in diabetic men. The subjects of this study were diabetic men suffering erectile dysfunction, non-responding to maximum dose of oral PDE5I. Mesenchymal bone marrow stem cells were aspirated and injected after preparation in both corpora cavernosa at 3, 9 o'clock position. Erectile function was assessed by the International Index of Erectile Function and penile Doppler study, before and after 6 months after injection. 4 patients out of 10 achieve hard erection adequate for satisfactory coitus, and 2 patients achieved penile hardness with addition of pharmacological therapy with sildenafil 100mg. Peak systolic velocity increased significantly in 4 patients (2 arteriogenic and 2 mixed erectile dysfunction), from 12∼22 cm/s to 32∼69 cm/s. Variations in end-diastolic velocity increased substantially in 2 patients with venogenic insufficiency alone at follow-up from 4∼5 cm /s to -4∼-3 cm/s. Despite promising stem cell treatment efficacy for patients with erectile dysfunction, more clinical studies and researches are still warranted.

Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women: a randomized, controlled trial.

Intrauterine adhesion is a major cause of female reproductive disorders. Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth, no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far. To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate, we conducted this randomized controlled clinical trial. Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter (control group) from February 2016 to January 2020. The per-protocol analysis included 140 participants: 72 in bone marrow stem cells-scaffold group and 68 in control group. The ongoing pregnancy occurred in 45/72 (62.5%) participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group (28/68, 41.2%) (RR=1.52, 95%CI 1.08-2.12, P=0.012). The situation was similar in live birth rate (bone marrow stem cells-scaffold group 56.9% (41/72) vs. control group 38.2% (26/68), RR=1.49, 95%CI 1.04-2.14, P=0.027). Compared with control group, participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis. The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed. In conclusion, transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates, and this therapy was relatively safe.

Autologous Bone Marrow Stem Cells in Patients With Critical Limb Ischaemia not Eligible for Revascularization: A Single Centre Experience.

We evaluated the use of autologus bone marrow stem cells transplantation in patients with critical limb ischaemia (CLI) not eligible for revascularization. Eighty consecutive patients candidate to amputation were enrolled in a single-centre retrospective study. The primary endpoint was defined as the amputation-free rate from stem cells transplantation. Secondary endpoints were the evaluation of transcutaneous oximetry and its predictive potential for probability of amputation and the evaluation of rest pain. Ankle brachial index, transcutaneous oxygen (TcpO2) and radiological imaging were performed at the enrolment and during the follow-up times. All patients were treated with auto transplant of bone marrow stem cells. Two patients died due to acute renal and acute respiratory failures. 19 patients were amputated from the thigh or leg. In total, 59 of 80 patients intended to thigh amputation saved the limb, preserving the plantar support. TcpO2 was found a predictive metric with an AUC equal to .763, and a threshold for a risk of amputation of 10% and 5% at the values ≤22.7 and ≤26.9mmHg, respectively. Auto transplant of bone marrow stem cells seems to be a safe and an efficient option for CLI not eligible to revascularizzation.

Efficacy of Activated Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Acute Myeloid Leukemia

To compare the efficacy of activated autologous bone marrow and peripheral blood hematopoietic stem cell transplantation (Auto-HSCT) and matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for the first complete remission of adult acute myeloid leukemia (AML-CR1). For 86 adult patients with first complete remission of AML who underwent auto-HSCT (41 cases) and MSD-HSCT (45 cases) in our hospital from June 2012 to June 2020, the patients were treated with modified MAC ［Malflane 160 mg/(m2·d), -3 days, Ara-C 2 g/(m2·2), -3 days 21∶00, -2 days 9∶00, CTX 60 mg/(kg·d),-3 d, -2 d］, the stem cells were activated by IL-2 (1 000 U/ mL), IFN-α (100 U/ mL) and IFN-γ (100 U/ml). The overall survival (OS), leukemia free survival (LFS), cumulative incidence of recurrence (CIR) and non-recurrence mortality (NRM) of patients with different types of transplantation were compared. The 3-year OS rates of Auto-HSCT group and MSD-HSCT group were 75% and 69.5%, and the 3-year LFS rates were 70.6% and 82.4%, respectively. There was no statisticaly significant difference in the 3-year OS rates of low risk, medium risk and high risk patients in the Auto-HSCT and MSD-HSCT group (90.2% vs 87.5%, 68.4% vs 68.8%, 28.6% vs 53.3%), the LFS rates of low risk, medium risk and high risk patients in the auto-HSCT and MSD-HSCT group were 90.2% and 87.5%(P=0.838), 71.8% and 91.7%(P=0.184), 0 and 67.5%(P=0.027), respectively. The NRM of Auto-HSCT and MSD-HSCT group were 4.9% and 20% (P=0.036), and CIR were 24.4% and 13.3% (P=0.188). Univariate analysis showed that the survival time of patients was significantly correlated with the number of CR courses and disease risk stratification (P=0.005, P=0.000). Cox multivariate analysis showed that disease risk stratification was an independent risk factor affecting OS (P=0.001). For adult patients with primary AML-CR1, Auto-HSCT is safe and effective. In the absence of sibling donor, Auto-HSCT can be regarded as an effective post-remission treatment for patients with intermediate risk AML-CR1.

Bone marrow stem cells incubated with ellipticine regenerate articular cartilage by attenuating inflammation and cartilage degradation in rabbit model.

Ellipticine (Ellip.) was recently reported to have beneficial effects on the differentiation of adipose-derived stem cells into mature chondrocyte-like cells. On the other hand, no practical results have been derived from the transplantation of bone marrow stem cells (BMSCs) in a rabbit osteoarthritis (OA) model. This study examined whether autologous BMSCs incubated with ellipticine (Ellip.+BMSCs) could regenerate articular cartilage in rabbit OA, a model similar to degenerative arthritis in human beings. A portion of rabbit articular cartilage was surgically removed, and Ellip.+BMSCs were transplanted into the lesion area. After two and four weeks of treatment, the serum levels of proinflammatory cytokines, i.e., tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2), were analyzed, while macroscopic and micro-computed tomography (CT) evaluations were conducted to determine the intensity of cartilage degeneration. Furthermore, immuno-blotting was performed to evaluate the mitogen-activated protein kinases, PI3K/Akt, and nuclear factor-κB (NF-κB) signaling in rabbit OA models. Histological staining was used to confirm the change in the pattern of collagen and proteoglycan in the articular cartilage matrix. The transplantation of Ellip.+BMSCs elicited a chondroprotective effect by reducing the inflammatory factors (TNF-α, PGE2) in a time-dependent manner. Macroscopic observations, micro-CT, and histological staining revealed articular cartilage regeneration with the downregulation of matrix-metallo proteinases (MMPs), preventing articular cartilage degradation. Furthermore, histological observations confirmed a significant boost in the production of chondrocytes, collagen, and proteoglycan compared to the control group. Western blotting data revealed the downregulation of the p38, PI3K-Akt, and NF-κB inflammatory pathways to attenuate inflammation. The transplantation of Ellip.+BMSCs normalized the OA condition by boosting the recovery of degenerated articular cartilage and inhibiting the catabolic signaling pathway.

Human-derived decellularized extracellular matrix scaffold incorporating autologous bone marrow stem cells from patients with congenital heart disease for cardiac tissue engineering.

Stem cells are used as an alternative treatment option for patients with congenital heart disease (CHD) due to their regenerative potential, but they are subject to low retention rate in the injured myocardium. Also, the diseased microenvironment in the injured myocardium may not provide healthy cues for optimal stem cell function. In this study, we prepared a novel human-derived cardiac scaffold to improve the functional behaviors of stem cells. Decellularized extracellular matrix (ECM) scaffolds were fabricated by removing cells of human-derived cardiac appendage tissues. Then, bone marrow c-kit+ progenitor cells from patients with congenital heart disease were seeded on the cardiac ECM scaffolds. Cell adhesion, survival, proliferation and cardiac differentiation on human cardiac decellularized ECM scaffold were evaluated invitro. Label-free mass spectrometry was applied to analyze cardiac ECM proteins regulating cell behaviors. It was shown that cardiac ECM scaffolds promoted stem cell adhesion and proliferation. Importantly, bone marrow c-kit+ progenitor cells cultured on cardiac ECM scaffold for 14 days differentiated into cardiomyocyte-like cells without supplement with any inducible factors, as confirmed by the increased protein level of Gata4 and upregulated gene levels of Gata4, Nkx2.5, and cTnT. Proteomic analysis showed the proteins in cardiac ECM functioned in multiple biological activities, including regulation of cell proliferation, regulation of cell differentiation, and cardiovascular system development. The human-derived cardiac scaffold constructed in this study may help repair the damaged myocardium and hold great potential for tissue engineering application in pediatric patients with CHD.

Influence of Autologous Bone Marrow Stem Cell Therapy on the Levels of Inflammatory Factors and Conexin43 of Patients with Moyamoya Disease.

Moyamoya disease is a medical condition that shows the typical characteristics like continuous and chronic thickening of the walls and the contraction of the internal carotid artery; as a result, the internal diameter of the artery gets narrowed. There are six phases of the disease ranging from I to VI (moyamoya vessels completely disappear, followed by the complete blockage of the arteries). Surgery is a commonly recommended treatment for the moyamoya disease. Our research study identifies the effect of autologous bone marrow stem cell therapy (ABMSCT) on the levels of inflammatory factors and Conexin43 (Cx43) protein in patients suffering from moyamoya. In our study, we have selected 52 moyamoya patients admitted to our hospital from 30 July 2019 to 10 February 2020. The control group (CG) was treated with superficial temporal artery to a middle cerebral artery (STA-MCA) bypass + encephalo-duro-myosinangiosis (EDMS). The experimental group (Exp. Grp) was treated with ABMSC. The cerebral vascular tissue of the patients was treated with hematoxylin-eosin (HE) staining. Immunohistochemical staining was used to identify the levels of Cx43 protein. The concentrations of vascular endothelial growth factor (VEGF), inflammatory factor interleukin-6 (IL6), interleukin-1β (IL1β), tumor necrosis factor (TNFα), and anti-inflammatory factor interleukin-1β (IL1β) were determined by enzyme-linked immunosorbent assay (ELISA). We have found that after treatment of the expression of Cx43 protein, the proportions of grade IV (7.7%), grade III (311.5%), and grade II (3.8%) patients in the Exp. Grp were lower than those in the CG. The proportion of grade I patients in the Exp. Grp (77%) was higher than that in the CG (38.5%). After treatment, the inflammatory factors IL6 (0.97 ± 0.82 pg/mL), IL1β (8.33 ± 1.21 pg/mL), and TNFα (1.73 ± 0.71 pg/mL) in the Exp. Grp were lower than those in the CG. The anti-inflammatory factor IL1β (15.09 ± 4.72 pg/mL) increased in the Exp. Grp compared with the CG (11.25 ± 3.48 pg/mL) post treatment. Intracranial infection, hydrocephalus, hemiplegia, and transient neurological dysfunction in the Exp. Grp were lower than those in the CG, with statistical differences (P < 0.05). Our study suggests that the treatment of autologous bone marrow stem cells (ABMSC) was beneficial to balance the inflammatory response of disorders, reduce the damage of vascular tissue in the brain, and regulate tissue repair by co-acting with various inflammatory factors as compared to traditional surgery. We conclude that the involvement of Cx43 in the occurrence and development of moyamoya. We also have found that the risk factors of intracranial infection after ABMSCT were less as compared to those after conventional surgery.

Human umbilical cord mesenchymal stromal cells promotes the proliferation and osteogenic differentiation of autologous bone marrow stem cells by secreting exosomes

ABSTRACT Fractures are frequently encountered diseases troubling the senior population, and the research on fracture repair and the exploration of effective treatment methods are of great significance. This study aimed to clarify the effect of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hUMSC-EVs) on the proliferation and osteogenic differentiation of autologous bone marrow stem cells (ABMSCs). The two kinds of cells were co-cultured firstly, 5-Ethynyl-2’- deoxyuridine (EDU) staining and alizarin red staining were used to detect the proliferation and osteogenic differentiation of ABMSCs. The exosomes of hUMSCs were subsequently extracted to process ABMSCs to further test the effect on the cells. The EDU positive rate of ABMSCs and Collagen II expression were elevated, whereas the TdT-mediated dUTP nick end labeling (TUNEL) positive rate and Matrix Metallopeptidase 13 (MMP13) were markedly decreased after the co-culture of hUMSCs and ABMSCs using Transwell chamber assays. The results indicated that hUMSCs could increase the proliferation of ABMSCs, reduce apoptosis, and promote matrix metabolism. The hUMSCs exosomes were separated and added to ABMSCs. As the exosomes content increased, the proliferation of ABMSCs increased simultaneously, and ABMSCs apoptosis decreased. Meanwhile, ABMSCs that migrated to the submembrane increased compared with untreated ABMSCs. Western blot, qPCR and immunofluorescence results revealed that increased exosomes contents promoted the expression of ABMSCs anabolic-related indicators gradually, while decreased the expression of catabolism-related indicators gradually. The previously described results indicated that hUMSCs promoted the proliferation and osteogenic differentiation of ABMSCs by secreting exosomes.

Combination use of core decompression for osteonecrosis of the femoral head: A systematic review and meta-analysis using Forest and Funnel Plots.

Objective This study evaluated the efficacy and safety of CD combined with bone marrow stem cells in the treatment of femoral head necrosis by systematic review and meta-analysis. Methodology. PubMed, The Cochrane Library, Embase, CNKI, Google Scholar and MEDLINE, etc. databases were searched for clinical randomized controlled trials (RCTs) comparing core decompression combined with autologous bone marrow mesenchymal stem cells versus core decompression alone in the treatment of femoral head necrosis. The retrieval period is from the establishment of each database to May 20, 2021. After literature was extracted and literature quality was evaluated, meta-analysis was conducted by using RevMan5.3 software. Results A total of 420 osteonecrosis of the femoral head 452 patients' data were collected from all studies. Compared with the core decompression alone group, the CD combined with bone marrow stem cell showed marked reduction in the Visual analog scale (VAS), enhanced Harris hip score (HHS) at 12 months and 24 months, slowed down the progression of the disease, decreased the number of hips conversed to total hip arthroplasty (THA) in the future. Conclusion Core decompression therapy is a very effective and safe treatment process used for ONFH. Moreover, CD combined autologous bone marrow stem cell transplantation can improve the survival rate of the necrotic head, reduce hip pain and delay the disease progression, the rate of THA postoperatively.

P.109: Long Term Outcomes After Autologous Bone Marrow Stem Cell Treatment in Diabetes Mellitus: Data From Unified National Electronic Health System 2014–2019

P.109: Long Term Outcomes After Autologous Bone Marrow Stem Cell Treatment in Diabetes Mellitus: Data From Unified National Electronic Health System 2014–2019

Scaffold With Natural Calcified Cartilage Zone for Osteochondral Defect Repair in Minipigs

Background: Long-term outcomes of current clinical interventions for osteochondral defect are less than satisfactory. One possible reason is an ignorance of the interface structure between cartilage and subchondral bone, the calcified cartilage zone (CCZ). However, the importance of natural CCZ in osteochondral defects has not been directly described. Purpose: To explore the feasibility of fabricating trilayer scaffold containing natural CCZ for osteochondral defects and the role of CCZ in the repair process. Study Design: Controlled laboratory study. Methods: The scaffold was prepared by cross-linking lyophilized type II collagen sponge and acellular normal pig subchondral bone with or without natural CCZ. Autologous bone marrow stem cells (BMSCs) of minipig were mixed with type II collagen gel and injected into the cartilage layer of the scaffold before operation. Thirty minipigs were randomly divided into CCZ (n = 10), non-CCZ (n = 10), and blank control (n = 10) groups. An 8 mm–diameter full-thickness osteochondral defect was created on the trochlear surface, and scaffold containing BMSCs was transplanted into the defect according to grouping requirements. At 12 and 24 weeks postoperatively, specimens were assessed by macroscopic observation, magnetic resonance imaging examination, and histological observations (hematoxylin and eosin, Safranin O–fast green, type II collagen immunohistochemical, and Sirius red staining). Semiquantitative cartilage repair scoring was conducted using the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) system and the O’Driscoll repaired cartilage value system. Results: The defects in the blank control and non-CCZ groups were filled with fibrous tissue, while the cartilage layer of the CCZ group was mainly repaired by hyaline cartilage at 24 weeks postoperatively. The superior repair outcome of the CCZ group was confirmed by MOCART and O’Driscoll score. Conclusion: The trilayer scaffold containing natural CCZ obtained the best repair effect compared with the non-CCZ scaffold and the blank control, indicating the importance of the CCZ in osteochondral tissue engineering. Clinical Relevance: This study demonstrates the necessity to reconstruct CCZ in clinical osteochondral defect repair and provides a possible strategy for osteochondral tissue engineering.

Abstract 23: Intracerebral Transplantation of Autologous Bone Marrow Stem Cell (BMSC) for Subacute Ischemic Stroke, Phase 1 Clinical Trial (RAINBOW Trial)

Background: Recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. We investigated the safety and feasibility of intracerebral transplantation of autologous BMSC in the subacute phase of stroke (RAINBOW trial). Several new aspects including cell labeling and tracking, socioecomonic analysis using QALY, and the use of human platelet lysate instead of fetal bovine serum were adopted. (UNIN ID: UMIN000026130) Methods/Design: This is a phase 1, open-label, uncontrolled, dose-response study enrolling adults with severe motor deficits (mRS&gt;3) 14 days after stroke. Approximately 50 mL of the bone marrow is extracted from the iliac bone of each patient 15 days or later from the onset, and BMSCs are cultured with allogeneic human platelet lysate (PL) and are labeled with superparamagnetic iron oxide for cell tracking using MRI. BMSCs are stereotactically administered around the area of infarction approximately 2 months from the ischemic stroke. Each patient will be administered a dose of 20 or 50 million cells. Neurological scoring, MRI for cell tracking, 18 F-fuorodeoxyglucose positron emission tomography, and 123 I-Iomazenil single photon emission computed tomography will be performed throughout 1 year after the administration. Results: All 7 patients have been successfully finished transplantation, and there was no severe adverse event in any of the patient regarding the surgical procedure nor cell quality. Favorable motor recoveries (change in mRS &gt; 1) are seen in 5 of 7 patients, and cell engraftment and migration to ischemic site was also observed. Discussion: This is a first-in-human trial to use labelled BMSC to the patients with subacute ischemic stroke. Intracerebral transplantation of autologous BMSC is safe and well tolerated. Cell migration to the ischemic boundary can clarify the therapeutic mechanisms.

INFLUENCE OF MESENCHYMAL STEM CELLS ON EFFICIENCY OF ANGIOGENESIS, STATE OF VASCULAR TONE, INTENSITY OF LIPID PEROXIDATION AND METABOLIC ACTIVITY OF CARDIOMYOCYTES IN EXPERIMENTAL MYOCARDIAL INFARCTION

In contrast to medical and surgical methods of treatment of coronary heart disease and its complications, cellular cardiomyoplasty is aimed at creating new cells and stable lineages of normally functioning heart tissue. Autologous mesenchymal bone marrow stem cells are a promising source for such cardiomyoplasty. To study the effect of stem cell myocardial transplantation on the processes of its post−infarction state, acute myocardial infarction in laboratory rats was experimentally modeled with subsequent transplantation of autologous mesenchymal stem cells of bone marrow and comparative study in blood serum of cardiovyocytes metabolic activity markers, neoangiogenesis, vessel tonus as well as myocardial lipid peroxidation. The cells were intravenously injected into the necrotized myocardium and left ventricle. The study found that regardless of the method of administration, stem cell transplantation contributes to a significant increase in angiogenic factors, i.e. nitrogen oxide and endothelial growth factor, a significant decrease in vasoconstrictor endothelin−1, the level of TBA−active products and haptoglobin, enzyme activity, namely cardiac ischemia markers, increase in ceruloplasmin. All this indicates positive effects: leveling ischemia by improving myocardial perfusion due to compensatory vasodilation, limiting the rate of lipid peroxidation and stimulating antioxidant factors, improving the energy balance of the myocardium by increasing the level of energy substrates and activation of their aerobic pathways. Thus, cellular cardiomyoplasty improves metabolism and prevents the process of post−ischemic myocardial remodeling. Key words: cardiomyoplasty, mesenchymal stem cells, myocardial infarction, myocardial metabolism.

SHORT-TERM RESULTS IN PATIENTS WITH REFRACTORY ANGINA TREATMENT USING STEM CELLS

Despite the large range of drugs and surgical interventions, there is currently a significant number of patients with angina, in whom the surgery is impossible for various reasons, and drug therapy is not effective enough. In contrast to these methods of treating coronary heart disease and its complications, cell cardiomyoplasty is aimed at creating new cells and stable lineages of normally functioning heart tissue. Autologous bone marrow mesenchymal stem cells are the promising source for such a cardiomyoplasty. To improve the treatment results in the patients suffered from coronary heart disease with refractory angina and heart failure, there was comparatively studied the effect of intravenous administration of autologous mesenchymal bone marrow stem cells on the effectiveness of myocardial remodeling at months 3 and 6, that was assessed by stenocardiography and echocardiography insufficiency, indices of quality of life and tolerance to physical activity. As a result, it was reliably established that the patients receiving autologous cell therapy in combination with traditional methods had a reduced incidence of anginal attacks, decreased functional class of heart failure and angina, improved left ventricular contractile function, improved exercise tolerance and quality of life. Thus, intravenous administration of autologous bone marrow mesenchymal stem cells to patients with chronic ischemic disease, which is manifested in refractory angina and complicated by heart failure is a safe alternative to other treatments and has its advantages. There has been an improvement in the heart pumping function and the life quality of patients. Key words: cardiomyoplasty, stem cells, heart failure, refractory angina.

Органосохранное хирургическое лечение некроза головки бедренной кости нетравматического генеза

Introduction Hip-salvage treatment in femoral head necrosis has a great social and economic importance.The number of hip joint replacements in young patients has been increasing. Purpose To evaluate the results of hip-preserving surgical interventions in the treatment of patients with non-traumatic femoral head necrosis. Materials and methods The study included 42 cases treated by minimally invasive core decompression of the femoral head and bone grafting, 22 cases of decompression and introduction of autologous bone marrow and mesenchymal stem cells into the core of necrosis, and six cases of using a titanium locking mesh implant. Results The follow-up time after surgery was up to 5 years. The survival rate of hip-reserving operations using cell technology to stimulate osteoregeneration were noticeably better than using bone grafting only in disease stages I, IIA, IIB, IIC. For femoral head osteonecrosis in stage IIIA, a titanium locking femoral head implant has been developed. It promotes regeneration and performs a supporting function. Conclusion The analysis of long-term results of these minimally invasive technologies has proven their efficacy and safety along with a low rate of complications.

The comparative analysis of different methods of autological stromal cells admission functional results in the treatment of patients with refractory angina

The aim of the study was to optimize the technique of cellular cardiomyoplasty in patients with refractory angina. The results of treatment of 75 patients with refractory angina who were hospitalized in the Emergency and Reconstructive Cardiac Surgery Department of the "V. Gusak Institute of Emergency and Reconstructive Surgery of NAMS of Ukraine" from 2007 to 2013 were analyzed. The intramyocardial implantation of autologous mesenchymal bone marrow stem cells in patients with chronic coronary heart disease and severe left ventricular failure is a safe method that can improve clinical data and prognosis. This method can be used as the first line of coronary heart disease treatment to prepare a patient for aortocoronary bypass. The injection of bone marrow stem cells in ischemic segments improves perfusion without induction of additional myocardial scarring. Unfortunately, currently there is no alternative to adequate therapy of patients with cardiac insufficiency, which is possessed of a minimal number of negative effects on one hand and could give patients a real chance for a positive effect of therapy on other one. Keywords: stem cells, cardiomyoplasty, heart failure, refractory angina.

Short-term and long-term results of intracoronary introduction of autologous mesenchymal stem cells in exertional angina pectoris

Purpose is to study the effectiveness of intracoronary introduction application of mesenchymal stem cells (MSC’s) in refractory angina pectoris.Material and methods. The study was based on the results founded by the investigation, treatment and dynamic follow-up results of 30 patients with refractory angina pectoris who underwent the stationary therapy in the department of Urgent and Recovery Cardiac surgery of SI «Institute of Urgent and Recovery Surgery named after V.K. Gusak of NAMS of Ukraine» from 2007 till 2014. We formed 2 groups; each of them included 15 patients: in the first group (a control one), the patients received only medicamental therapy; the second group received intracoronary administration of autologous MSC’s. According to NYHA (New York Heart Association) classification, all the patients had II-IV functional class of chronic heart failure (CHF). All the patients earlier went through the different revascularization surgeries. Mesenchymal autologous bone marrow stem cells were received according to the standard method in the laboratory of cellular and tissue cultivation of SI «Institute of Urgent and Recovery Surgery named after V.K. Gusak of NAMS of Ukraine». Using the local anesthesia with catheter application in the coronary vessel mouth was implemented a transplant in the dose of 10 million cells.Results. During the control examination, a clinical improvement was observed in all the patients; it was expressed in the quality of life increase according to the Minnesota Questionnaire (MLHFQ); in a decrease of heart failure grade according to NYHA, and tolerance growth to physical exercise during the treadmill test. The maximal effect, by the way, was developed in month and had been holding on during the 9-12 months. Thus if the quality of life before applying the transplantation of autologous MSC was 58+1,8 points; after the 3 months this rate was 32±2,2 points (by p&lt;0,05); but after the I year, it was 37±2,1 points and was progressively decreased in the future. During the ultrasound imaging in the first group was mentioned decrease of left ventricle (LV) ejection fraction (EF) till 23,2±5,2% during the whole study; in the second group, it was observed an EF increase from 31,2±7,1 to 37,4±5,2% by p&lt;0,05 and to the deadline of 6 months it began to decrease. In this period of time the patients reduced the doses of taken medicines; it was mentioned tolerance intensification to the physical exercises that we approved with the help of treadmill test. During the cardiac mapping with the help of navigation system CARTO XP we observed that in 6 months the amplitude of unipolar signal increased from 7,8-8,7 MB to 9,0-9,4 MB in the front-lateral zone; and from 5,3-12,0 to 7,9-14,1 MB in the b posteroseptal correspondingly; it tells about the improvement of electromechanical association and improvement of working function as well as myocardium perfusion. In three years during the control investigation, it was mentioned a negative dynamics in comparison with the baseline results. Conclusions. As we see, the first experience of intracoronary introduction of autologous MSC in patients with refractory angina pectoris showed the raise of myocardium functional reserve that was reflected in the improvement of life quality; reduction of antianginal agent doses; raise of LV EF; as well as in the amplitude of unipolar myocardium signal increase in the MSC introduction zone.