Mesenchymal stem cells (MSCs) have been transplanted to successfully treat a variety of diseases and conditions. The benefit of using MSCs is their ability to self-renew and differentiate into a variety of specialized cell types, such as osteoblasts (cells contributing to bone formation), chondrocytes (cartilage cells), adipocytes (fat cells), myocardiocytes (the muscle cells that make up the cardiac muscle), and neurons (nervous system cells).
MSCs have shown the ability to modulate the immune response and therefore reduce local inflammation. They can be isolated from a variety of sources, such as adipose (fat) tissues, tendons, peripheral blood, umbilical cord blood and bone marrow. MSCs derived from bone marrow have been among the most successfully transplanted cells, offering therapeutic benefits.
Bone marrow was used as a source for MSCs in three different animal models of disease studies in which MSC transplantation was performed as detailed below and they will be published in future issues of Cell Transplantation.
MSCs promote fracture healing in rats Researchers in Hong Kong, China, who hypothesized that systemic and localized administration of bone-marrow-derived MSCs could promote fracture healing, assigned 48 adult male rats modeled with femoral fractures to four treatment groups. Two groups received MSCs, with one administered systemically and a second locally, four days after the rats were modeled with femoral fractures. The other two rat groups did not receive MSCs.
Five weeks after fracture modeling, it was found that the two groups receiving MSCs, either systemically or locally, had fracture gaps united while fracture gaps were still present in the two groups that did not receive MSCs. Both the locally injected and systemic injected groups demonstrated similar and indistinguishable fracture uniting patterns. However, the presence of generated osteoblasts in the systemically administered group was higher than in the locally injected group. "These findings provide critical insight for developing MSC-based therapies as systemic injection of allogeneic (other donated) MSCs may be a novel treatment method for promoting fracture repair," concluded the researchers.
This study is currently freely available on-line as an unedited early e-pub: Citation: Huang, S.; Xu, L.; Zhang, Y.; Sun, Y.; Li, G. Systemic and local administration of allogeneic bone marrow derived mesenchymal stem cells promotes fracture healing in rats. Cell Transplant. Appeared or available on-line: February 2, 2015.
MSCs found to be therapeutic in treating mice modeled with intrapulmonary acute lung injury
Bone marrow-derived MSCs have previously been used to successfully treat acute lung injury. However, questions remained with regard to whether bone marrow-derived MSCs could successfully treat both intra-pulmonary and extra-pulmonary acute lung injury. Sepsis induces extra-pulmonary acute lung injury while pneumonia induces intra-pulmonary acute lung injury. Inflammatory responses are common in both cases, however sepsis-induced acute lung injury is always accompanied by endothelial damage and multiple organ dysfunction. Researchers in Nanjing, P.R. China, who transplanted green fluorescent protein (GFP) labeled MSCs intravenously into mice modeled with the two forms of acute lung injury to evaluate their distribution (by detection of GFP) and therapeutic effects, found that the MSCs attenuated acute lung injury and inhibited lung inflammation in both models. More MSCs were recruited to the lungs of those modeled with intra-pulmonary injury, however, than those with extra-pulmonary acute lung injury. Also, the benefit of the MSCs was greater in the former group. "Our data suggest that MSCs may have greater potential for treating intra-pulmonary than extra-pulmonary acute lung injury because of the superior recruitment of MSCs into the lungs of mice with intra-pulmonary acute lung injury," concluded the researchers. "This finding may contribute to the clinical use of MSCs for the treatment of acute lung injury".
This study is currently freely available on-line as an unedited early e-pub: Citation: Liu, L.; He, H.; Liu, A.; Xu, J.; Han, J.; Chen, Q.; Hu, S.; Xu, X.; Huang, Y.; Guo, F.; Yang, Y.; Qiu, H. Therapeutic effects of bone marrow-derived mesenchymal stem cells in models of pulmonary and extrapulmonary acute lung injury. Cell Transplant. Appeared or available on-line: February 18, 2015.
MSCs attenuate fibrosis in rat models of ureteral obstruction
Chronic kidney disease (CKD), which contributes to end-stage renal disease and mortality, is characterized by renal fibrosis and can be caused by unilateral ureteral obstruction (UUO). In this study, researchers from Brazil evaluated the effects of MSCs in eight groups of female rats modeled with UUO, following transplantation shortly after obstruction. Two groups were examined seven days post-transplantation and two groups examined 14 days post-transplantation. The researchers found that intravenous administration of MSCs improved fibrosis progression, inflammation, cell proliferation and epithelial-mesenchymal transition, indicating a potential tool for preventing CKD.
"The MSCs primarily have a supporting function," concluded the researchers. "This is most likely due to secreting growth factors and cytokines. If the MSC-derived secreted factors can reduce CKD progression, this may have great clinical relevance as a therapy and also potentially overcome problems associated with allogeneic MSC administration, such as immune incompatibility and tumorigenesis" .
This study is currently freely available on-line as an unedited early e-pub: Citation: da Silva, A. F.; Silva, K.; Reis, L. A.; Teixeira, V. P. C.; Schor, N. Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Medium Attenuate Fibrosis in an Irreversible Model of Unilateral Ureteral Obstruction. Cell Transplant. Appeared or available on-line: February 18, 2015.
"Bone marrow-derived MSCs can differentiate into a variety of cell types in the body," says Maria Carolina de Oliveira Rodrigues of the University of São Paulo, Brazil and section editor for Cell Transplantation. "Since these cells are so versatile, they are ideal candidates to treat various pathologies. More studies are needed to elucidate the mechanisms by which these cells exert their therapeutic effect - either by cell replacement or trophic and anti-inflammatory effects".