Mesenchymal Stem Cells (MSC), from the early development of mesodermal and ectoderm, are important members of the family of stem cells. Mesenchymal Stem Cells are adult stem cells owning replication capacity and multilineage differentiation potential which are non-terminally differentiated cells and whose features are similar to that of interstitial cells, endothelial cells and epithelial cells. In vitro specific conditions, Mesenchymal stem cells can divide into multiple organizations such as fat, cartilage, bone, muscle, tendon, nerve, liver, myocardium, islet β-cells and endothelial cells. They have multilineage differentiation potential after the continuous passage culture and cryopreservation. Both autologous transplantation and allogeneic mesenchymal stem cells will not cause the immune response to hosts.
The typical human mesenchymal stem cells have the following characteristics: fibroblast-like, swirling wall growth, cells having not significantly change, higher expression of stromal cells marked CD29, CD105 and CD44, no expression of hematopoietic cell markers CD34 and CD45. Under the appropriate conditions, it can different into cartilage, bone, and fat cells.
Mesenchymal stem cells are first found in the bone marrow , and next in many kinds of organizations of human body in the development process. At present, mesenchymal stem cells used are usually umbilical cord-derived. This tissue-derived mesenchymal stem cells not only maintain the biological characteristics of mesenchymal stem cells, but also have the following advantages: ① The stem cells or progenitor cells from umbilical cord have more proliferation and differentiation capability . ② Immune cells are naive and have lower functional activities, so they will not trigger an immune response and cause Graft-versus-host disease. ③ stem cells are easier to be separated, high purity, non-tumor cell contamination.④ It is easy to control for the culture system is amplified.⑤ It can be made into seed cells in frozen and used several times for a small loss.⑥ The risk of contraction and spread from latent viruses and pathogens is lower. ⑦ When collected on maternal and neonates, it will have not any damage and injury. ⑧ The acquisition is convenient, storage and transport are simple, less ethics controversy.
In view of having the potential of multidirectional differentiation and the capacity of hematopoiesis and promotion hematopoietic stem cells implantation and the regulation of the immune and simple operation of isolation and culture, the mesenchymal stem cells are gaining the attention. With mesenchymal stem cells related technologies more sophisticated, clinical studies have been carried out in many countries. As seed cells, they are mainly used in the clinical treatment of a variety of refractory disease that can not be naturally repaired by tissue cells due to organ damage; as regulatory T cells, they are used in the treatment of immune rejection and autoimmune diseases.
The initial clinical study was conducted in 1995 by Lazarus et al. They collected the autologous MSC of blood cancer patients in remission which were cultured 4 to 7 weeks in vitro and through intravenous injected into a patient's body. The patients were divided into 3 groups which were given different doses of MSC. If toxic effects were not observed after injection, it would suggest that MSC for transplantation in the treatment was safe and reliable. Later the autologous MSC clinical reports gradual increased, involving hematopoietic reconstitution after radiotherapy and chemotherapy, graft-versus-host disease(GVHD) and heart diseases, which have proved that intravenous injection is safe and reliable.
However, the application of autologous mesenchymal stem cells gradually exposed inconvenience such as: great individual differences of amplification ability, potential risk of contamination of tumor cells, long culture time which restricted the use of autologous mesenchymal stem cells. In 2004, Le Blanc and others reported the first successfulness of semi-allogeneic mesenchymal stem cell transplantation in the treatment of GVHD, then reported the effectiveness of the allogeneic mismatched mesenchymal stem cell transplantation in the treatment of GVHD, not requiring strict matching. Then there were some reports on allogeneic MSC which mainly derived from bone marrow, fat, periodontal in the treatment of GVHD without matching and promotion hematopoietic reconstitution .
The FDA has approved nearly 60 clinical trials, mainly includes the following several aspects.
1. Hematopoietic stem cell transplantation: enhancement hematopoietic function; promotion the hematopoietic stem cell grafts implanted; treatment of graft versus host disease.
2. Repair tissue injury: bone, cartilage and joint damage, heart damage; Liver injury; Spinal cord injury and neurological diseases.
3. Autoimmune diseases: systemic lupus erythematosus (sle), scleroderma, inflammatory enteritis, etc.
4. the carrier of gene therapy.
The treatment of graft versus host disease and crohn's disease has entered the stage of phase III in the United States. We have begun to use mesenchymal stem cell to treat some refractory diseases clinically in China，such as spinal cord injury, cerebral palsy, muscular dystrophy, amyotrophic lateral sclerosis and systemic lupus erythematosus, systemic sclerosis, crohn's disease, stroke, diabetes, diabetic foot, cirrhosis of the liver, etc.. According to preliminary clinical reports, mesenchymal stem cells for the treatment of these diseases has had obvious curative effect.
Mesenchymal stem cells has brought new hope in regenerative medicine，and further research and clinical application of mesenchymal stem cells will be benefit mankind in the near future. Mesenchymal stem cells from the umbilical cord will be the most prospect pluripotent stem cells in clinical application for strong differentiation potential, proliferation, low immunogenicity, extensive materials conveniently, and non-restrictions on ethical questions and easy industrialized preparation etc..