Implantation Of Autologous Bone Marrow Cells Research Articles

Therapy with bone marrow mesenchymal stem cells in bone regeneration in children with osteonecrosis secondary to sickle cell disease.

This study aimed to describe the evolution of bone regeneration in children with hip osteonecrosis associated with sickle cell disease, treated with bone marrow-derived mesenchymal stem cell implants at the Professor Edgar Santos University Hospital Complex. A non-randomized clinical trial was conducted with 48 patients of both sexes, aged between 11 and 18years, diagnosed with femoral head osteonecrosis secondary to sickle cell disease. Patient selection was based on strict criteria, including confirmed diagnosis of sickle cell anemia and a stage of osteonecrosis compatible with the proposed treatment. Bone regeneration assessment was performed through radiographic examinations and magnetic resonance imaging, following the Ficat & Arlet criteria and the Salter-Thompson classification. Statistical analysis revealed a significant association between the patients' age and positive treatment outcomes, suggesting that autologous bone marrow cell implantation is a safe and effective approach in the early stages of osteonecrosis. The majority of patients (87.5%) reported complete pain relief, while 10.42% experienced significant symptom improvement. Only one patient (2.08%) did not observe improvement. The results indicate that cell therapy can regenerate or slow the progression of bone necrosis, reducing the need for more invasive surgical procedures. The study demonstrates the potential of bone marrow-derived mesenchymal stem cell implantation in treating hip osteonecrosis in children with sickle cell disease, emphasizing the importance of long-term monitoring of bone structure stability.

Efficacy of treatment of lower-limb critical ischaemia by methods of indirect revascularization

The study was aimed at comparing the efficacy of implantation of autologous bone marrow cells with that of revascularizing osteotrephination in treatment of lower limb chronic critical ischaemia in patients with a poor distal vascular bed. We analysed the results of comprehensive examination and treatment of a total of 60 patients presenting with lower limb chronic critical ischaemia due to atherosclerotic lesions of the femoropopliteal-tibial segment. According to the technology of treatment, the patients were divided into two statistically homogenous groups of 30 people each. Group One patients underwent standard revascularizing osteotrephination and Group Two patients in accordance with the original technique received intramuscular implantation of 40 ml of autologous bone marrow cells, with this volume distributed in 2-ml injections to 20 points of the muscles of the crus and femur along the internal and external surface. The use of the original technique of treatment made it possible to achieve the clinical status in the form of moderate or minimal improvement 6 months after bone marrow cells implantation in 29 (96.7%) patients and after 12 months in 28 (93.3%) patients, whereas after revascularizing osteotrephination in 25 (83.3%) and 20 (66.7%) patients, respectively. In the remote period after 12 months, the limb was saved in 28 (93.3%) and 26 (86.7%) patients in Group Two and Group One, respectively. The patients of the second group as compared with those of the first group after 12 months demonstrated a statistically significant increase in the physical health component by 19.8% and the mental health component by 9.8%. Implantation of autologous bone-marrow cells in chronic critical limb ischaemia is pathogenetically substantiated and makes it possible to optimize the results of treatment of patients.

One-year results of the treatment of critical lower limb ischemia with indirect revascularization methods

The OBJECTIVEwas to compare the efficiency of autologous bone marrow cell implantation and lumbar sympathectomy in the treatment of chronic critical lower limb ischemia.MATERIAL AND METHODS. The complex examination and treatment of 66 patients with critical lower limb ischemia, divided into 2 statistically homogeneous groups, was analyzed. The first group underwent sympathectomy, and the second – autologous bone marrow cell transplantation.RESULTS. After 1 year, in patients of the second group, compared with the first, the clinical status increased by 51.5 %, the number of amputations decreased by 3 %, the physical component of health increased by 7.9 %, the psychological component – by 17.7 %.CONCLUSION. The autologous bone marrow cell transplantation was pathogenetically substantiated and effective.

Autologous Bone Marrow Cell Stimulation and Allogenic Chondrocyte Implantation for the Repair of Full-Thickness Articular Cartilage Defects in a Rabbit Model.

The aim of this study was to evaluate the results of autologous bone marrow cell stimulation and allogenic chondrocyte implantation using 3-dimensional gel-type fibrin matrix in an animal model. Eighteen rabbits were divided into 2 treatment groups. One group was treated with a microfracture and covering of it with gel-type fibrin (AutoBMS; n = 9), and the other group was treated with allogenic chondrocytes mixed gel-type fibrin at the cartilage defect (AlloCI; n = 9). The control group was untreated cartilage defect at the other side knee of each object. Twelve weeks after treatment, the cartilage was evaluated using the International Cartilage Repair Society (ICRS) scoring system, immunohistochemical staining, and modified O'Driscoll grading system. The ICRS scores were similar in the AutoBMS (9.44 ± 2.44) and the AlloCI (9.33 ± 1.67) groups ( P < 0.05). Immunohistochemical staining confirmed higher expression of cartilaginous collagen for both groups. The average difference (AutoBMS, 31.89 ± 6.54; AlloCI, 32.89 ± 5.25) in the modified O'Driscoll scores appeared to be nonsignificant ( P > 0.05); however, both treatment groups showed significantly higher scores with respect to their control group (18.45 ± 1.65; 18.97 ± 1.58) ( P < 0.05). This experimental study suggests autologous bone marrow cells stimulation and implantation of allogenic chondrocytes are both useful methodologies for regenerating hyaline-like cartilage in full-thickness cartilage defects in animal model.

LONG-TERM RESULTS OF TRANSMYOCARDIAL LASER REVASCULARIZATION COMBINED WITH IMPLANTATION OF AUTOLOGOUS BONE MARROW MONONUCLEAR FRACTION IN THE TREATMENT OF CHRONIC ISCHEMIC HEART DISEAS

Aim. Clinical and instrumental assessment of long-term results of autologous bone marrow cells (BMC) implantation in laser channels in surgery of ischemic heart disease with diffuse and distal coronary disease.Materials and Methods. In the period of 2007–2008 35 CHD patients with diffuse and distal coronary disease underwent BMC implantation in laser channels during coronary artery bypass grafting (CABG). The control group consisted of 29 patients. All patients in this group underwent only direct myocardial revascularization (DMR). In the long-term period we examined only 30 patients of the first group. Clinical and instrumental assessment of the method efficacy was carried out in 2 weeks, 6 months and 6 years after surgery.Results. FC (NYHA) mean value in indirect revascularization group significantly decreased from 2.57 ± 0.61 preoperatively to 1.77 ±0.66 in6 months after surgery (p = 0.043). After 6 years FC (NYHA) was not significantly changed – 1.84 ± 0.42 (p = 0.053). Perfusion scintigraphy revealed a slight decrease of stable perfusion defect (SPD) in the immediate postoperative period, a more pronounced reduction of SPD in 6 months after surgery. The average value of SPD before surgery was 20.46 ± 10.75%, in 2 weeks after the operation – 19.07 ± 9.69%, in 6 months after surgery – 15.22 ± 9.49%. In the long-term period (6 years) SPD was 14.8 ± 8.43% (p = 0.047). A similar pattern was observed in the analysis of transient perfusion defect: baseline – 30 ± 2.2%, in 6 months – 15 ± 1.3%, in the long term period – 20 ± 6.1% (p = 0.047). The average value of left ventricular ejection fraction (LVEF) before surgery was 55 ± 10.4%, in 2 weeks after the operation – 55.7 ± 9.3%, in 6 months – 56.7 ± 10%, after 6 years – 54 ± 12%. The dynamics is unauthentic (p = 0.068).Conclusion. BMC implantation in laser channels in addition to CABG is a safe and effective method of surgical treatment in case of CABG inability. The effect of indirect revascularization is formed in the first 6 months after surgery and remains at the same level for 6 years.

Preliminary Results of Multiple Epiphyseal Drilling and Autologous Bone Marrow Implantation for Osteonecrosis of the Femoral Head Secondary to Sickle Cell Disease in Children.

Sickle cell disease (SCD) is the most common cause of osteonecrosis of the femoral head (ONFH) during childhood. The natural history of ONFH in SCD is poor with progression to femoral head collapse and deformity that ultimately may lead to hip osteoarthritis. Multiple epiphyseal drilling with autologous bone marrow implantation may enhance the mechanism of osteogenic repair. The purpose of this study was to describe early clinical and radiographic outcomes in pediatric patients with ONFH secondary to SCD after multiple epiphyseal drilling and AMBI. Nine boys and 2 girls (14 hips) with a mean age of 12.7 years (range, 9.7-18 y) at the time of surgery were evaluated. All patients were followed for at least 1 year after surgery and the mean duration of follow-up was 25 months (range, 12-47 mo). Clinical outcome was assessed by the pain domain from the Children's Hospital Oakland Hip Evaluation Scale and by hip range of motion. The extent of femoral head involvement was assessed by measuring the arc of necrosis and the amount of collapse on anteroposterior and frog lateral radiographs. The University of Pennsylvania system was used to assess the osteonecrosis stage. Wilcoxon signed-rank tests were used to compare radiographic and clinical variables. Compared with preoperative measures, multiple epiphyseal drilling with AMBI resulted in significant improvement in pain (P=0.0010), internal hip rotation (P=0.0005), external hip rotation (P=0.0010), and flexion (P=0.0015). The amount of lateral collapse (P=0.4609), anterior collapse (P=0.4258), and the arc of necrosis (P=0.2251) were not significant after surgery. The majority of the hips had either improvement in the Steinberg stage of disease (4/14 hips) or no further progression (7/14 hips) at the latest follow-up. There were no surgical complications. Multiple epiphyseal drilling with autologous bone marrow cell implantation allows for short-term clinical improvement and limits radiographic progression of ONFH associated with SCD in children with minimal morbidity.

The role of “cell therapy” in osteonecrosis of the femoral head

Background and purpose — The value of core decrompression for treatment of osteonecrosis of the femoral head (ONFH) is unclear. We investigated by a literature review whether implantation of autologous bone marrow aspirate, containing high concentrations of pluripotent mesenchymal stem cells, into the core decompression track would improve the clinical and radiological results compared with the classical method of core decompression alone. The primary outcomes of interest were structural failure (collapse) of the femoral head and conversion to total hip replacement (THR).Patients and methods — All randomized and non-randomized control trials comparing simple core decompression with autologous bone marrow cell implantation into the femoral head for the treatment of ONFH were considered eligible for inclusion. The methodological quality of the studies included was assessed independently by 2 reviewers using the Cochrane Collaboration tool for assessing risk of bias in randomized studies. Of 496 relevant citations identified, 7 studies formed the basis of this review.Results — The pooled estimate of effect size for structural failure of the femoral head favored the cell therapy group, as, in this treatment group, the odds of progression of the femoral head to the collapse stage were reduced by a factor of 5 compared to the CD group (odds ratio (OR) = 0.2, 95% CI: 0.08–0.6; p = 0.02). The respective summarized estimate of effect size yielded halved odds for conversion to THR in the cell therapy group compared to CD group (OR = 0.6, 95% CI: 0.3–1.02; p = 0.06).Interpretation — Our findings suggest that implantation of autologous mesenchymal stem cells (MSCs) into the core decompression track, particularly when employed at early (pre-collapse) stages of ONFH, would improve the survivorship of femoral heads and reduce the need for hip arthroplasty.

Abstract 3305: Sustained production of a soluble IGF-I receptor by gutless adenovirus - transduced host cells protects from tumor growth in the liver .

Abstract The IGF-I receptor (IGF-IR) plays an important role in malignant disease by increasing cancer cell survival and promoting metastasis. It is presently the target of several drugs in clinical trials. Gene therapy is currently being developed for cancer treatment using different nanoparticle vectors designed to deliver therapeutic genes that could induce cell death, increase sensitivity to chemotherapy, block angiogenesis or enhance the anti-cancer immunological response. Previously, we have shown that the implantation of autologous bone-marrow stromal cells producing a soluble form of IGF-IR (sIGFIR) inhibited experimental liver metastasis of several tumor types in mice. Here we evaluated the utility of adenovirus-based gene delivery for generating therapeutically effective plasma levels of this decoy. A third generation gutless adenovirus was selected to deliver the sIGFIR gene because of its reduced immunogenicity and preferential tropism for the liver, the main source of endocrine IGF-1. We found that HEK-293 cells transduced by this, but not by control adenoviruses, secreted soluble receptor protein that blocked IGF-I-induced tumor cell migration, proliferation and survival in vitro. Following virus injection in vivo, viral DNA was detectable by PCR in several host organs, particularly the liver, and this resulted in the production of measurable sIGFIR plasma levels for up to 21 days post injection. In mice producing virus-encoded sIGFIR, experimental liver metastasis was inhibited, indicating that sIGFIR levels were therapeutically effective. The results show that adenovirus-based delivery of inhibitory soluble proteins can provide an effective strategy for blockade of cancer cell growth. Citation Format: Ni Wang, Yifan Lu, Amelie Pilotte, Maxime Pinard, Rénald Gilbert, Bernard Massie, Pnina Brodt. Sustained production of a soluble IGF-I receptor by gutless adenovirus - transduced host cells protects from tumor growth in the liver . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3305. doi:10.1158/1538-7445.AM2013-3305

Sustained production of a soluble IGF-I receptor by gutless adenovirus-transduced host cells protects from tumor growth in the liver

The IGF-I receptor (IGF-IR) has an important role in malignant disease and is the target of several drugs presently in clinical trials. Gene therapy has been explored as cancer treatment, mainly for delivery of genes that induce cell death or enhance the immunological response to cancer. Previously, we have shown that the implantation of autologous bone-marrow stromal cells producing a soluble form of IGF-IR (sIGFIR) inhibited experimental liver metastasis of several tumor types in mice. Here, we evaluated the utility of adenovirus-based gene delivery for generating therapeutically effective plasma levels of this decoy. We constructed a third generation gutless adenovirus expressing sIGFIR and found that HEK-293 cells transduced by this, but not control adenoviruses, secreted soluble receptor protein that blocked IGF-I-induced tumor cell migration, proliferation and survival in vitro. Following virus injection in vivo, viral DNA was detectable by PCR in several host organs, particularly the liver, and this resulted in the production of measurable sIGFIR plasma levels for up to 21 days post injection. In mice producing virus-encoded sIGFIR, experimental liver metastasis was inhibited, indicating that sIGFIR levels were therapeutically effective. The results show that adenovirus-based delivery of inhibitory soluble proteins can provide an effective anticancer strategy.

Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: Five year follow-up of a prospective controlled study

To determine the efficacy of bone marrow cell implantation into the necrotic lesion of the femoral head on clinical symptoms and the progression of osteonecrosis of the femoral head in comparison with core decompression. We studied nineteen patients and twenty four hips with early stage osteonecrosis of the femoral head. The hips were allocated to either core decompression only or core decompression and implantation of bone marrow cells. Both patients and assessors were blind with respect to treatment group assignment. The primary outcomes were clinical symptoms and disease progression. Bone marrow implantation afforded a significant reduction in pain and in joint symptoms and reduced the incidence of fractural stages. At 60 months, eight of the eleven hips in the control group had deteriorated to the fractural stage whereas only three of the thirteen hips in the bone marrow graft group had progressed to that stage. Survival analysis showed a significant difference in the time to failure between the two groups at 60 months. Patients had only minor side-effects after the treatments. This long term follow-up study confirmed that implantation of autologous bone marrow cells in the necrotic lesion might be an effective treatment for patients with early stages of osteonecrosis of the femoral head.

Neovascularization induced by autologous bone marrow cell implantation in peripheral arterial disease

Neovascularization induced by autologous bone marrow cell implantation in peripheral arterial disease

Prediction of Limb Salvage after Therapeutic Angiogenesis by Autologous Bone Marrow Cell Implantation in Patients with Critical Limb Ischemia

Despite advances in therapeutic angiogenesis by bone marrow cell implantation (BMCI), limb amputation remains a major unfavorable outcome in patients with critical limb ischemia (CLI). We sought to identify predictor(s) of limb salvage in CLI patients who received BMCI. Nineteen patients with CLI who treated by BMCI were divided into two groups; four patients with above-the-ankle amputation by 12 weeks after BMCI (amputation group) and the remaining 15 patients without (salvage group). We performed several blood-flow examinations before BMCI. Ankle-brachial index (ABI) was measured with the standard method. Transcutaneous oxygen tension (TcPO2) was measured at the dorsum of the foot, in the absence (baseline) and presence (maximum TcPO2) of oxygen inhalation. (99m)technetium-tetrofosmin ((99m)Tc-TF) perfusion index was determined at the foot and lower leg as the ratio of brain. Maximum TcPO2 (p = 0.031) and (99m)Tc-TF perfusion index in the foot (p = 0.0068) was significantly higher in the salvage group than in the amputation group. Receiver operating characteristic (ROC) curve analysis identified maximum TcPO2 and (99m)Tc-TF perfusion index in the foot as having high predictive accuracy for limb salvage. Maximum TcPO2 and (99m)Tc-TF perfusion index in the foot are promising predictors of limb salvage after BMCI in CLI.

Therapeutic angiogenesis by autologous bone marrow cell implantation together with allogeneic cultured dermal substitute for intractable ulcers in critical limb ischaemia

Therapeutic angiogenesis by autologous bone marrow cell implantation improves blood supply in patients with critical limb ischaemia. In addition, allogeneic cultured dermal substitute is effective for intractable ulcers. The present study determined the effectiveness of bone marrow cell implantation combined with allogeneic cultured dermal substitute in treating severely ischaemic ulcers. We treated eight consecutive patients with severely ischaemic ulcers using this procedure. Stromal cells aspirated from bone marrow were processed to obtain suspensions of mononuclear cells, platelets and endothelial progenitor cells and immediately injected intramuscularly into the lower leg and around the wound, on which allogeneic cultured dermal substitute was applied and changed weekly. Skin ulcers were subsequently closed by skin grafting, if necessary. Angiogenesis was confirmed by postoperative analyses such as ankle-brachial pressure index, angiography, thermography and (99m)Technetium-Tetrofosmin perfusion scintigraphy. Above- or below-knee amputation was avoided in all patients and wounds were completely closed in six of them. These results indicate that this combined therapy effectively treated ischaemic ulcers. Since the incidence of this condition might increase in the future, this therapeutic approach should play an important role in the preservation of ischaemic limbs.

The effect of bone marrow mononuclear cells on vascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head

ObjectiveWe examined whether implantation of autologous bone marrow mononuclear cells (BM-MNC) can augment neovascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head. MethodsSixty-five 28-week-old male New Zealand white rabbits were divided into group I (left untreated, N=20), group II (core decompression, N=20) and group III (core decompression+autologous bone marrow cells implantation, N=25) after receiving an established inductive protocol for inducing steroid-associated ON. Four weeks later, these rabbits were euthanized, bilateral femora were dissected for micro-CT-based microangiography to assess vascularization, and then the osteonecrotic changes and repair processes were examined histopathologically. ResultsQuantitative analysis showed that new vessel formation in group III was significantly greater compared with other groups at 4 weeks after treatment. Penetrating capillary vessels number vessels number in group III (44.5±5.11) was significantly larger than that of group II (11.4±2.46) and group I (3.10±0.33) (p<0.01). The histologic and histomorphometric analysis revealed that the new bone volume was significantly higher in the group III than in the group I and II, 4 weeks after treatment. ConclusionIn this animal model, a combination of bone marrow mononuclear cells and core decompression enhance the neovascularization and the osteoinductive ability, resulting in bone regeneration. These findings confirm the preliminary clinical results obtained in humans that the implantation of bone marrow mononuclear cells is an effective and feasible method for treating early osteonecrosis.

Early results of autologous mononuclear bone marrow cell implantation in nontraumatic avascular necrosis of the femoral head

We evaluated early clinical and radiologic results of core decompression combined with autologous mononuclear bone marrow cell implantation for early stage nontraumatic avascular necrosis of the femoral head. The study included nine patients (1 female, 8 males, mean age 46.5 years; range 33 to 59 years) with stage I-II nontraumatic avascular necrosis of the femoral head, according to the Steinberg classification. Bone marrow-derived CD34 cells were injected through a core decompression channel into the femoral head. Clinical assessment included a visual analog scale (VAS), Harris hip score, and the WOMAC Osteoarthritis Index. Radiologically, femoral head collapse, narrowing of the coxofemoral joint space, and the size of the osteonecrotic area were assessed. The mean follow-up was 27.2 months (range 24 to 38 months). Pre- and postoperative (24th month) evaluations showed that the mean VAS score and the WOMAC Osteoarthritis Index decreased from 3.4+/-0.4 to 1.2+/-0.6, and from 33+/-3 to 11+/-6, respectively, with an increase in the Harris hip score (from 54 to 92). Preoperatively, two patients were Steinberg I-B, four were I-C, and three were II-A. Finally, all the patients were stage 0 except for one patient who regressed to I-A. None of the patients exhibited femoral head collapse or narrowing of the coxofemoral joint space. Autologous mononuclear bone marrow cell implantation relieves articular pain, prevents the progression of osteonecrosis, and hence subchondral fractures. Therefore, it may be treatment of choice particularly in stage I-II avascular necrosis of the femoral head.

Early results of autologous mononuclear bone marrow cell implantation in nontraumatic avascular necrosis of the femoral head

Early results of autologous mononuclear bone marrow cell implantation in nontraumatic avascular necrosis of the femoral head

Tratamento da Osteonecrose da Cabeça Femoral com celulas progenitoras autólogas em anemia falciforme

OBJETIVO: Avaliação da segurança e eficácia do uso de células progenitoras autólogas da medula óssea (CMMO) no tratamento da Osteonecrose da Cabeça Femoral (OCF) de pacientes portadores de anemia falciforme. MÉTODOS: Foram estudados 8 pacientes portadores de anemia falciforme, com OCF nos estágios I e II (classificação de Ficat e Arlet). As CMMO retiradas da crista ilíaca posterior foram concentradas e reinfundidas na área central da osteonecrose. Os principais parâmetros avaliados foram segurança, sintomas clínicos e progressão da doença, através da avaliação clínica (Harris Hip Score) e radiológica. RESULTADOS: A maior parte dos pacientes (7 em 8) referiu melhora dos sintomas após o tratamento. Não houve complicações durante o procedimento anestésico e cirúrgico. A medida do escore (Harris Hip Score) no pré-operatório foi 78,5 +/- 6,2 pontos, com aumento significativo destes valores no pós-operatório (98,3 +/- 2,5 pontos) (p&lt; 0,001). As avaliações radiográficas e os parâmetros celulares foram favoráveis. CONCLUSÃO: O implante autólogo de CMMO parece ser seguro e eficaz no tratamento dos estágios iniciais da OCF em pacientes falciformes. Embora os resultados iniciais sejam promissores, sua interpretação é limitada pelo número de pacientes avaliados e o período curto de duração do seguimento pós-operatório. Necessita-se estender o grupo em estudo e os parâmetros celulares avaliados.

Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial)

Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD). We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 x 10(6) cells/0.1 mL, n = 9), high dose (2 x 10(6) cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 +/- 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 +/- 182 s in controls and 393 +/- 136 s in BM-treated patients, and changed after 6 months to 383 +/- 223s and 464 +/- 196 s [BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11-0.74, P = 0.014]. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4-10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02-0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation. Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.

Comparative evaluation of long-term clinical efficacy with catheter-based percutaneous intramyocardial autologous bone marrow cell implantation versus laser myocardial revascularization in patients with severe coronary artery disease

Catheter-based percutaneous laser myocardial revascularization (PMR) and intramyocardial direct bone marrow (BM) cell implantation have been investigated to treat patients with severe coronary artery disease (CAD). In both therapeutic approaches, direct local myocardial injury might be a common mechanism to induce therapeutic angiogenesis. We studied the long-term clinical outcome in 16 patients with severe CAD who received either catheter-based PMR (n = 8) or intramyocardial autologous BM cell implantation (n = 8) as guided by electromechanical mapping. There were no significant differences in the baseline characteristics and the number of injection versus the number of laser pulse delivered between the 2 groups (P > .05). As compared with baseline, the New York Heart Association functional class and the number of anginal episodes were significantly reduced at 3- and 6-month follow-up in both BM and PMR groups (P < .05). However, the improvement in the New York Heart Association class and the reduction in anginal episodes at 18 months were only persisted in the BM group (P < .05) but not in the PMR group (P > .05). Furthermore, there were significant improvements in exercise time at 6- and 18-month follow-up, and the extent of stress-induced perfusion single-photon emission computed tomography defects at 6-month follow-up in BM group, as compared with baseline (all P < .05), but not in the PMR group (all P > .05). As compared with baseline, there were no significant changes in the total quality of life scores during follow-up in both groups (all P > .05). The results of this study demonstrated that the catheter-based intramyocardial autologous BM cell implantation might be more effective than PMR in improving symptoms and exercise capacity in patients with severe CAD. The beneficial effect of direct intramyocardial injection was over and beyond those noted in patients treated with PMR, suggesting a potential direct therapeutic effect of BM cells, rather than local myocardial injury alone on chronic ischemic myocardium.

Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells: Five-year follow-up

Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells: Five-year follow-up