Chee-Yin Wong

Cryopreserved mesenchymal stromal cell treatment is safe and feasible for severe dilated ischemic cardiomyopathy.

BACKGROUND AIMS Bone marrow (BM) mesenchymal stromal cells (MSC) represent a novel therapy for severe heart failure with extensive myocardial scarring, especially when performed concurrently with conventional revascularization. However, stem cells are difficult to transport in culture media without risk of contamination, infection and reduced viability. We tested the feasibility and safety of off-site MSC culture and expansion with freeze-controlled cryopreservation and subsequent rapid thawing of cells immediately prior to implantation to treat severe dilated ischemic cardiomyopathy. METHODS We recruited three consecutive patients with end-stage ischemic heart failure with evidence of full-thickness myocardial scarring. MSC was isolated from 20 mL BM aspiration, expanded and cryopreserved using 10% dimethyl sulfoxide (DMSO). Cells were transported in a cryoshipper. Patients underwent concurrent coronary artery bypass graft (CABG) with intramyocardial MSC injection. RESULTS The cell viability after thawing exceeded 90% for all samples. The supernatant was free from bacterial and fungal growth. All patients underwent the procedure safely. There were no arrhythmias noted. There was significant improvement in cardiac function and volume, resolution of scarring and increased wall thickness for all patients on cardiac magnetic resonance imaging at 6 months compared with baseline. The magnitude of improvement was more than was expected with CABG alone. Patients remained well at 1 year. CONCLUSIONS Rate-controlled freezing with 10% DMSO is a safe, feasible and practical method of cryopreserving MSC for cell storage and transportation without risk of contamination or cell death. Direct MSC injection may be beneficial as an adjunct to cardiac revascularization.

Intramyocardial and intracoronary autologous bone marrow-derived mesenchymal stromal cell treatment in chronic severe dilated cardiomyopathy

BACKGROUND AIMS Mesenchymal stromal cells (MSC) may improve cardiac function following myocardial infarction. MSC can differentiate into cardiomyocytes and endothelial cells while exerting additional paracrine effects. There is limited information regarding the efficacy of route for MSC treatment of severe dilated cardiomyopathy (DCM). The aim of this study was to demonstrate the clinical safety, feasibility and efficacy of direct intramyocardial and intracoronary administration of autologous bone marrow-derived MSC treatment for no-option patients with chronic severe refractory DCM. METHODS Ten symptomatic patients with DCM and refractory cardiac function, despite maximum medical therapy, were selected. Five had ischemic DCM deemed unlikely to benefit from revascularization alone and underwent bypass operations with concurrent intramyocardial MSC injection (group A). Two patients had previous revascularization and three had non-ischemic DCM and received intracoronary MSC injection (group B). RESULTS Group A and B patients received 0.5-1.0 × 10(6) and 2.0-3.0 × 10(6) MSC/kg body weight, respectively. All patients remained alive at 1 year. There were significant improvements from baseline to 6 and 12 months in left ventricular ejection fraction and other left ventricular parameters. Scar reduction was noted in six patients by 12 months. CONCLUSIONS Autologous bone marrow MSC treatment is safe and feasible for treating chronic severe refractory DCM effectively, via intracoronary or direct intramyocardial administration at prescribed doses.

In vitro differentiation of mesenchymal stem cells into mesangial cells when co‐cultured with injured mesangial cells

Mesangial cells are one of the three major cell types of the kidney glomerulus that provide physical support for the glomerular capillary lumen of the kidney. Loss of mesangial cells due to pathologic conditions, such as glomerulonephritis and diabetic nephropathy, can impair renal function. Mesenchymal stem cells (MSC) are attractive candidates for kidney repair therapy since they can enhance recovery and protect against kidney failure. MSC can differentiate into mesangial cells in vivo. We have investigated the ability of MSC to differentiate into mesangial cells in vitro; they were co‐cultured with oxidant‐injured mesangial cells before being analysed by flow cytometry and for contractility. MSC co‐cultured with injured mesangial cells had a mesangial cell‐like morphology and contracted in response to angiotensin II. They expressed CD54− CD62E+ in direct contrast to the CD54+ CD62E− of pure MSC. In conclusion, MSC can differentiate into mesangial cells in vitro when co‐cultured with injured mesangial cells.

Relocation of cryopreserved umbilical cord blood samples using a high-capacity dry shipper to a new laboratory: a cord blood banking experience.

Processed umbilical cord blood (UCB) must be stored at cryogenic temperature at all times to maintain the quality and viability of the cells. However, a challenge is presented in the form of moving a large number of cryopreserved UCB samples to a new location. In this report, we share our experience on relocating more than 100,000 units of cryopreserved UCB samples stored in 12 liquid nitrogen freezers (LNFs) to our new laboratory.