Mesenchymal stem cells (MSCs) represent a promising tool for new clinical concepts in supporting cellular therapy. Bone marrow (BM) was the first source reported to contain MSCs. However, for clinical use, BM may be detrimental due to the highly invasive donation procedure and the decline in MSC number and differentiation potential with increasing age. More recently, umbilical cord blood (UCB), attainable by a less invasive method, was introduced as an alternative source for MSCs. Another promising source is adipose tissue (AT). We compared MSCs derived from these sources regarding morphology, the success rate of isolating MSCs, colony frequency, expansion potential, multiple differentiation capacity, and immune phenotype. No significant differences concerning the morphology and immune phenotype of the MSCs derived from these sources were obvious. Differences could be observed concerning the success rate of isolating MSCs, which was 100% for BM and AT, but only 63% for UCB. The colony frequency was lowest in UCB, whereas it was highest in AT. However, UCB-MSCs could be cultured longest and showed the highest proliferation capacity, whereas BM-MSCs possessed the shortest culture period and the lowest proliferation capacity. Most strikingly, UCB-MSCs showed no adipogenic differentiation capacity, in contrast to BM- and AT-MSCs. Both UCB and AT are attractive alternatives to BM in isolating MSC: AT as it contains MSCs at the highest frequency and UCB as it seems to be expandable to higher numbers.

Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue.

https://www.exphem.org/article/S0301-472X(05)00364-4/pdf

Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood.

https://journals.sagepub.com/doi/pdf/10.3727/096368915X689622

Clinical Trials with Mesenchymal Stem Cells: An Update:

Cell-based cardiac repair offers the promise of rebuilding the injured heart from its component parts. Work began with committed cells such as skeletal myoblasts, but recently the field has expanded to explore an array of cell types, including bone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and both mouse and human embryonic stem cells. A related strategy for cardiac repair involves cell mobilization with factors such as cytokines. Translation of cell-based approaches to the clinic has progressed rapidly, and clinical trials using autologous skeletal myoblasts and bone marrow cells are under way. Many challenges remain before the vision of healing an infarct by muscle regeneration can be realized. Future research is likely to focus on improving our ability to guide the differentiation of stem cells, control their survival and proliferation, identify factors that mediate their homing and modulate the heart's innate inflammatory and fibrotic responses.

Regenerating the heart.

Background Mesenchymal stromal cells (MSCs, “adult stem cells”) have been widely used experimentally in a variety of clinical contexts. There is interest in using these cells in critical illness, however, the safety profile of these cells is not well known. We thus conducted a systematic review of clinical trials that examined the use MSCs to evaluate their safety. Methods and Findings MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (to June 2011), were searched. Prospective clinical trials that used intravascular delivery of MSCs (intravenously or intra-arterially) in adult populations or mixed adult and pediatric populations were identified. Studies using differentiated MSCs or additional cell types were excluded. The primary outcome adverse events were grouped according to immediate events (acute infusional toxicity, fever), organ system complications, infection, and longer term adverse events (death, malignancy). 2347 citations were reviewed and 36 studies met inclusion criteria. A total of 1012 participants with clinical conditions of ischemic stroke, Crohn's disease, cardiomyopathy, myocardial infarction, graft versus host disease, and healthy volunteers were included. Eight studies were randomized control trials (RCTs) and enrolled 321 participants. Meta-analysis of the RCTs did not detect an association between acute infusional toxicity, organ system complications, infection, death or malignancy. There was a significant association between MSCs and transient fever. Conclusions Based on the current clinical trials, MSC therapy appears safe. However, further larger scale controlled clinical trials with rigorous reporting of adverse events are required to further define the safety profile of MSCs.

/pdf/safety-of-cell-therapy-with-mesenchymal-stromal-cells-14iwpqlsza.pdf

Safety of Cell Therapy with Mesenchymal Stromal Cells (SafeCell): A Systematic Review and Meta-Analysis of Clinical Trials

Sixty-nine patients who underwent primary percutaneous coronary intervention within 12 hours after onset of acute myocardial infarction were randomized to receive intracoronary injection of autologous bone marrow mesenchymal stem cell or standard saline. Several imagining techniques demonstrated that bone marrow mesenchymal stem cells significantly improved left ventricular function.

http://www.kumc.edu/Documents/msctc/Chen-Am%20J%20Cardiol.%20(2004).pdf

Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction.

Background The infarct size determines the long-term prognosis of patients with acute myocardial infarction (AMI). There is a growing interest in repairing scar area by transplanting bone marrow stem cells. However, effectiveness of intracoronary injection of bone marrow mesenchymal stem cells (BMSCs) in patients with AMI still remains unclear.Methods Sixty-nine patients with AMI after percutaneous coronary intervention (PCI) were randomly divided into intracoronary injection of BMSCs (n=34) and saline (control group, n=35) groups. Serial single positron emission computer tomography (SPECT), cardiac echo and cardiac electromechanical mapping were done at the designed time intervals until six months after transplantation of BMSCs or injection of saline. Results The proportion with functional defect decreased significantly in the BMSCs patients after three months [(13±5)%] compared with that pre-transplantation [(32±11)%] and the control group [(28±10)%] at three month follow-up (P0.05, respectively). Wall movement velocity over the infracted region increased significantly in the BMSCs group [(4.2±2.5) cm/s vs (2.2±1.3) cm/s, P0.05], but not in the control group [(2.2±1.5) cm/s vs (2.7±1.7) cm/s, P0.05]. Left ventricular ejection fraction (LVEF) three months after transplantation in BMSCs group increased significantly compared with that pre-implantation and with that of the control group at three months post-injection [(67±11)% vs (49±9)% and (53±8)%, P0.05 respectively]. SPECT scan results showed that perfusion defect was improved significantly in BMSCs group at three-month follow-up compared with that in the control group [(134±66)cm2 vs (185±87)cm2, P0.01]. At the same time, left ventricular end-diastolic volume [(136±31) ml vs (162±27) ml, P0.05] and end-systolic volume [(63±20) ml vs (88±19) ml, P0.05] decreased synchronously. The ratio of end-systolic pressure to end-systolic volume [P_ syst/ESV, (2.84±1.30) mmHg/ml vs (1.72±1.23) mmHg/ml, P0.05] increased significantly. Cardiac electromechnical mapping demonstrated significant improvement at three months after implantation of BMSCs compared with that pre-injection in both cardiac mechanical capability as left line local shorting [LLS, (11.29±1.64)% vs (7.32± 1.86)%, P0.05] and electrical property as left ventricular endocardial unipolar voltage [UV, (10.38±1.12) mV vs (7.61±1.09) mV, P0.01]; perfusion defect decreased from (36.2±6.2) % to (20.3±5.31)% (P0.01). Twenty-four-hour electrocardiographic monitoring demonstrated no arrhythmias occurred at three-months follow-up.Conclusions The transplantation of BMSCs might improve the cardiac function and it is safe and feasible with no deaths or malignant arrhythmias.

Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction.

OBJECTIVE To determine the mid-term effects of cutting balloon angioplasty (CBA) on in-stent restenosis. METHODS A total of 69 patients with in-stent restenosis were divided into 2 groups randomly: cutting balloon angioplasty and plain old balloon angioplasty. The mechanisms of restenosis and dilation results were determined by quantitative coronary angiography and intravascular ultrasound. Follow-up was performed. RESULTS The procedural success rate was 100% without death and acute closure. One patient experienced dissection at the distal end of the stent and needed another stent. The mean follow-up period was 6.7 +/- 2.3 months. The final re-restenosis rate was 15% and 18% at 3 months and 6 months respectively, markedly lower than after plain old balloon angioplasty (38% and 43%). Acute gain by intravascular ultrasound (IVUS) was 1.72 +/- 0.52 mm after cutting balloon angioplasty, higher than 1.15 +/- 0.54 mm after plain old balloon angioplasty. The lumen diameter late loss in the cutting balloon group was 0.26 +/- 0.05 mm and 0.38 +/- 0.06 mm at 3 months and 6 months respectively, significantly lower than for those in conventional balloon group (0.78 +/- 0.19 mm and 0.89 +/- 0.16 mm, respectively, P < 0.001). As shown by IVUS, the main mechanism of cutting balloon angioplasty was marked reduction of plaque area without significant increase of vessel area (less vessel trauma). CONCLUSION Cutting balloon angioplasty is feasible and effective for the treatment of in-stent restenosis with less vessel trauma.

Wu-wang Fang

Papers

Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction.

Improvement of cardiac function after transplantation of autologous bone marrow mesenchymal stem cells in patients with acute myocardial infarction.

Cutting balloon angioplasty for treatment of coronary in-stent restenosis: immediate results and 6-month outcomes.