Autologous bone marrow derived stem cell therapy in patients with type 2 diabetes mellitus-defining adequate administration methods

AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bone marrow mononuclear cells were separatedand purified using centrifugation. These cells were then infused in a total of 21 patients comprising three groups of 7 patients each. Cells were infused into the superior pancreaticoduodenal artery(Group Ⅰ), splenic artery(Group Ⅱ) and through the peripheral intravenous route(Group Ⅲ). Another group of 7 patients acted as controls and a sham procedure was carried out on them(Group Ⅳ). The cells were labelled with the PET tracer F18-FDG to see their homing and in vivo distribution. Data for clinical outcome was expressed as mean ± SE. All other data was expressed as mean ± SD. Baseline and post treatment data was compared at the end of six months, using paired t-test. Cases and controls data were analyzed using independent t-test. A probability(P) value of < 0.05 was regarded as statistically significant. Measures of clinical outcome were taken as the change or improvement in the following parameters:(1) C-peptide assay;(2) HOMA-IR and HOMA-B;(3) reduction in Insulin dose; subjects who showed reduction of insulin requirement of more than 50% from baseline requirement were regarded as responders; and(4) reduction in HbA 1c. RESULTS All the patients, after being advised for healthy lifestyle changes, were evaluated at periodical intervals and at the end of 6 mo. The changes in body weight, body mass index, waist circumference and percentage of body fat in all groups were not significantly different at the end of this period. The results of intra-group comparison before and after ABMSCT at the end of six months duration was as follows:(1) the area under C-peptide response curve was increased at the end of 6 mo however the difference remained statistically non-significant(P values for fasting C-peptide were 0.973, 0.103, 0.263 and 0.287 respectively and the P values for stimulated C-peptide were 0.989, 0.395, 0.325 and 0.408 respectively for groups Ⅰ?to Ⅳ);(2) the Insulin sensitivity indices of HOMA IR and HOMA B also did not show any significant differences(P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for groups Ⅰto Ⅳ);(3) Group Ⅰshowed a significant reduction in Insulin dose requirement(P < 0.01). Group Ⅱ patients also achieved a significant reduction in Insulin dosages(P = 0.01). The Group Ⅰand Group Ⅱ patients together constituted the targeted group wherein the feeding arteries to pancreas were used for infusing stem cells. Group Ⅲ, which was the intravenous group, showed a non-significant reduction in Insulin dose requirement(P = 0.137). Group Ⅳ patients which comprised the control arm also showed a significant reduction in Insulin dosages at the end of six months(P < 0.05); and(4) there was a non-significant change in the Hb A1 c levels at the end of 6 mo across all groups(P = 0.355, P = 0.351, P = 0.999 and P = 0.408 respectively for groups Ⅰto Ⅳ). CONCLUSION Targeted route showed a significant reduction in Insulin requirement at the end of six months of study period whereas the intravenous group failed to show reduction.

Minimally manipulated autologous adherent bone marrow cells (ABMCs):a promising cell therapy of spinal cord injury

Spinal cord injury（SCI）is a devastating ailment that results in drastic life style alterations for the patients and their family members（Mc Donald and Sadowsky,2002）.Damage post injury causes necrosis,edema,hemorrhage and vasospasm.Post injury,secondary damage is caused by ischemia,

HIM_(1) AND HIM4, TWO MONOCLONAL ANTIBODIES POTENTIALLY USEFUL FOR AUTOLOGOUS BONE MARROW TRANSPLANTATION IN CHRONIC MYELOGENOUS LEUKEMIA

We developed two complement-fixing MoAbsHIMand HIM(murine)that were specifically reac-tive with chronic myelogenous leukemia (CML) cells.They were capable of fixing human or rabbit com-plement and suitable for CML cells purging of re-mission marrow from CML patients.HIMreactedwith majority leukemic cells form 7 out of 10 CMLpatients by complement-mediated cytotoxicity(C’MC)assay(positive cells 80%—90%),HIMreacted withmajority CML cells from 4 out of 5 CML by C’MCassay(positive cells 80%—90%).Treatment withHIMor HIMand human C’was capable of lysing97% of K562,U937,HL-60 and CML cells in a 20fold excess of unrelated cells by indirect FITC+EBstain.Using limited dilution culture,incubation withHIMand C’produced 1.5 logs inhibition of growthin K562 cells,and 1.9 logs in U937 cells,and withHIMand C’produced 2.9 logs inhibition in HL-60cells and 3.0 logs in U937 cells.Both MoAbs cocktailwas shown 1.8 logs in K562 cells and 3.2 logs in U937cells.They were no suppression on the growth o

Autologous bone marrow infusion via portal vein combined with splenectomy for decompensated liver cirrhosis: A retrospective study

BACKGROUND In a previous study,autologous bone marrow infusion(ABMI)was performed in patients with decompensated liver cirrhosis(DLC)and acquired immunodefi-ciency syndrome and achieved good results,but whether splenectomy affected outcome was unclear.AIM To investigate the efficacy of ABMI combined with splenectomy for treatment of DLC.METHODS Eighty-three patients with DLC were divided into an intervention group(43 cases)and control group(40 cases)according to whether splenectomy was performed.The control group was treated with ABMI through the right omental RESULTS After ABMI,the prothrombin time,serum total bilirubin levels,ascites volume and model for end-stage liver disease score in both groups were significantly lower,while the albumin levels were significantly higher than before ABMI(P<0.01),but there were no significant differences between the groups(P>0.05).After ABMI,the white blood cell and platelets counts in both groups were significantly higher than before ABMI(P<0.01),and the counts in the intervention group were significantly higher than in the control group(P<0.01).After ABMI the CD4+and CD8+T cell counts in both groups were significantly higher than before ABMI(P<0.01).The CD8+T cell counts in the intervention group increased continuously and the increase had a shorter duration compared with control group.CONCLUSION ABMI through the portal vein in patients with DLC can significantly improve liver synthetic and secretory functions,and splenectomy promotes improvement of bone marrow hematopoietic and cellular immune functions.

The effectiveness of the mononuclear fraction of autologous bone marrow in the treatment of experimental chronic limb ischemia

Objective To study of the effectiveness of using autologous mononuclear fraction of bone marrow for the treatment of chronic limb ischemia. Methods Results of autologous mononuclear fraction of bone marrow in 90 laboratory Wistar rats on a background of creating chronic limb ischemia was presented. Sampling was carried out from the bone marrow of the femur of the animal. The mononuclear fraction of bone marrow autologous 4 × 106 cells in a volume of 200 microliter were injected into the ischemic limb of the two points,in each of which 100 microliter:(1)Paravessel directly below the inguinal ligament at the level of the sacroiliac joint in the area of the anatomical location of collaterals in the projection of the internal iliac artery and its branches;(2)Intramuscularly in gastrocnemius muscle anterior-lateral surface of the middle third of the leg. Results In the experimental group of rats treated with autologous mononuclear fraction of bone marrow,the level of microcirculation compared with the intact group of animals on day 21 was higher than 6. 1% by day 28% ~ 31. 2%; compared with the control group-day 10 increased by 111% at day 21,85. 7% on day 28% ~ 97%. Conclusion Proposed method of treating pathogenically justified and can be recommended for use in clinical practice in the treatment of patients with chronic obliterating diseases of lower limb arteries.

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.

Transplantation of autologous bone marrow mononuclear cells for patients with lower limb ischemia

Background Many treatment options for lower limb ischemia are difficult to apply for the patients with poor arterial outflow or with poor general conditions. The effect of medical treatment alone is far from ideal, especially in patients with diabetic foot. A high level amputation is inevitable in these patients. This study aimed to explore the effect of transplantation of autologous bone marrow mononuclear cells on the treatment of lower limb ischemia and to compare the effect of intra-arterial transplantation with that of intra-muscular transplantation. Methods In this clinical trial, 32 patients with lower limb ischemia were divided into two groups. Group 1 （16 patients with 18 affected limbs） received transplantation of autologous bone marrow mononuclear cells by intra-muscular injection into the affected limbs; and group 2 （16 patients with 17 affected limbs） received transplantation of autologous bone marrow mononuclear cells by intra-arterial injection into the affected limbs. Rest pain, coldness, ankle/brachial index （ABI）, claudication, transcutaneous oxygen pressure （tcPO2） and angiography （15 limbs of 14 patients） were evaluated before and after the mononuclear cell transplantation to determine the effect of the treatment. Results Two patients died from heart failure. The improvement of rest pain was seen in 76.5% （13/17） of group 1 and 93.3% （14/15） of group 2. The improvement of coldness was 100% in both groups. The increase of ABI was 44.4% （8/18） in group 1 and 41.2% （7/17） in group 2. The value of tcPO2 increased to 20 mmHg or more in 20 limbs. Nine of 15 limbs which underwent angiography showed rich collaterals. Limb salvage rate was 83.3% （15/18） in group 1 and 94.1% （16/17） in group 2. There was no statistically significant difference in the effectiveness of the treatment between the two groups. Conclusions Transplantation of autologous bone marrow mononuclear cells is a simple, safe and effective method for the treatment of lower limb ischemia, and the two approaches for the implantation, intra-muscular injection and intra-arterial injection, show similar results.

Modified technique of advanced core decompression for treatment of femoral head osteonecrosis

BACKGROUND Osteonecrosis of the femoral head(ONFH)is a destructive condition most commonly affecting young and middle-aged patients.The leading consequence of ONFH is often a significant articular disability.Effective joint-preserving surgical treatments are urgently needed for patients with early stage ONFH when outcomes of treatment are in general better than the advanced stage disease.AIM To introduce a new surgery procedure called percutaneous expanded core decompression and mixed bone graft technique,which is a new way of jointpreserving surgical treatments.METHODS The clinical data of 6 patients with ONFH diagnosed and treated with the procedure called percutaneous expanded core decompression and mixed bone graft technique at The First Hospital of Qiqihar from March 2013 to August 2019 were retrospectively analyzed;the follow-up ended in December 2019.RESULTS There were 6 male patients with an average age of 43 years in our study.Gratifying results have been obtained from the comparison of Harris hip score,visual analogue scale,and imaging examination before and after operation.CONCLUSION This new modified technique is simple,safe,and reliable.No serious perioperative complications were observed in our cases.Advantages of the single blade expandable reamer are obvious.The adjuvant substance is inexpensive and easy to obtain.Thus,this technique is an effective joint-preserving surgical treatment for patients with early stage of ONFH.

The Mobilization of Autologous Bone Marrow Stem Cells in the Treatment of Heart Failure with Chinese Medicine

Heart failure （HF） is a severe heart disease. The use of autologous bone marrow stem cells （BMCs） mobilization in the treatment of HF has been a hot topic to research both in Western medicine and Chinese medicine （CM）. There are many clinical trials and experiments on study of BMCs mobilization for HF therapy, including integrative medicine. The effect of BMCs mobilization is favorable for cardiac repair, while some advantages of CM support the advanced study of its application in BMCs mobilization to treat HF. In addition, with mechanisms of autologous BMCs mobilization for the treatment of HF that will be revealed in the future, especially stem cells niches, integrative medicine would play an important role in this clinical thought of therapy model gradually. Simultaneously, CM should adapt the new approaches of stem cells progresses on HF treatment as holding characteristics of itself.

Effect of intracoronary autologous bone marrow mononuclear cells transplantation on arrhythmia in canines

Objective To observe the survival and the differentiation of grafted bone marrow cells(BM-MNCs)in host myocardium.To observe whether BM-MNCs transplantation can potentially cause arrhythmia and whether the BM-MNCs transplantation can alter the spatial distribution of connexins,important mediator for arrhythmia gen-