Human-derived UCB stem cell transplant has positive therapeutic effects on specific lung and heart disorders

Nov 24 2009

Two separate studies published in the current issue of Cell Transplantation (18:8), - now freely available on-line at http://www.ingentaconnect.com/content/cog/ct - have shown that transplanted human-derived umbilical cord blood (UCB) stem cells transplanted in an animal model had positive therapeutic effects on specific lung and heart disorders the animal models.

"Human UCB-derived MSCs (mesenchymal stem cells) have been successfully isolated, cultivated and been shown to differentiate into various cell types, such as osteoblasts, chondrocytes, adipocytes, stromal cells, skeletal cells, endothelial cells and neural cells and even lung-specific cells in vitro," said corresponding author of the first study, Dr. Won Soon Park from the Samsung Medical Center, Seoul, Korea. "It is not known, however, if human UCB-derived MSCs can differentiate into lung-specific cell types in vivo."

To find out, the researchers investigated the therapeutic benefits of transplanting human umbilical cord blood (UCB) mensenchymal stem cells (MSCs) into newborn laboratory rats with oxygen-deprived lung injury. They found that MSCs have a protective effect against hyperoxia-induced lung injury, likely due to anti-inflammatory effects. The researchers noted that their findings are expected to have important therapeutic potential for the currently untreatable hyperoxic neonatal lung disease, or bronchopulmonary dysplasia (BPD), in premature human infants. The easy availability of UCB is an associated benefit.

Dr. Park noted that the optimal route for transplantation had not previously been determined.

"An injured lung produces soluble factors that cause MSCs to proliferate and migrate toward an injured lung," he explained. "But it has been unclear if the local, intratracheal administration of MSCs is comparable to, or better than systemic transplantation."

The researchers found that the intratracheal, rather than the intraperitoneal transplantation of human UCB-derived MSCs, significantly attenuated the hyperoxia-induced lung injury, such as decreased alveolarization and fibrosis. Survival rate was not improved by the MSC transplants, however. Questions remain over whether the donor cells exert a therapeutic effect by inducing direct tissue repair and regeneration of damaged cells, said the researchers.

A research team in Germany evaluated the feasibility and efficacy of autologous (self-donated) umbilical cord blood mononuclear cell (UCMNC) transplantation on right ventricular (RV) function in a large animal model of chronic RV overload. Their study examined the potential therapeutic role of UCMNCs in treating one of the most common cyanotic congenital heart defects in the Tetralogy of Fallot (TOF), a group of congenital heart defects.

They found that the transplant enhanced diastolic properties, likely through blood vessel growth (angiogenesis). The authors noted that UCMNCs have already been shown to be therapeutic agents in patients suffering from major hematological disorders.

"Surgical repair is inevitable and aims to normalize pulmonary blood flow by correcting the abnormal anatomy of the right ventricular outflow tract, but no experimental approach has been conducted to study the potential of stem cell treatment in RV volume overload," said corresponding author Dr. Can Yerebakan of the University of Rostock, Rostock, Germany.

They concluded that UCMNC transplantation was "feasible and safe" and seemed to "positively influence the diastolic properties of the RV under chronic volume overload."

Three months post-transplantation into laboratory sheep, the researchers were able to observe an alteration in the RV function, which is one of the long-term determinants of morbidity and mortality after TOF correction.

"We observed significantly enhanced capillary formation in the cell group, which yielded the possible explanation of better diastolic function achieved by cell transplantation," said Dr. Yerebakan. "This finding indicates the potential importance of UCB for RV modeling after infundibulotomy."

"These two studies add to the plethora of potential uses for UBC, ranging from possible treatments for neurological disorders, such as stroke and Alzheimer's disease to Diabetes, and now the repair of damaged heart and lungs," commented Section Editor Dr. Julio Voltarelli, professor of clinical medicine and clinical immunology in the Head, Bone Marrow Transplantation Unit at the University Hospital (Hospital das Cl-nicas), University of S-o Paulo, Brazil.