Autologous Mesenchymal Stroma Cells Are Superior to Allogeneic Ones in Bone Defect Regeneration.
Anna E RappRonny BindlAnnika ErbacherAnne KruchenMarkus RojewskiHubert SchrezenmeierIngo MüllerAnita IgnatiusPublished in: International journal of molecular sciences (2018)
The application of autologous mesenchymal stem cells (MSC) for the treatment of bone defects requires two invasive procedures and several weeks of ex vivo cell expansion. To overcome these limitations, the administration of allogeneic MSC may be attractive, because they are anticipated to be immunoprivileged. Because preclinical studies using various animal models are conflicting with respect to the efficacy of allogeneic MSC, we investigated whether autologous and allogeneic human MSC (hMSC) are equally effective in regenerating bone in a humanized mouse model resembling the human immune system. Applying autologous and allogeneic hMSC in critically sized femoral defects, we found that allogeneic hMSC elicited a mild immune response early after implantation, whereas early angiogenic processes were similar in both treatments. At later healing time points, the transplantation of allogeneic hMSC resulted in less bone formation than autologous hMSC, associated with a reduced expression of the osteogenic factor Runx2 and impaired angiogenesis. We found by species-specific staining for collagen-type-1α2 that MSCs of either source did not synthesize new bone matrix, indicating an indirect contribution of transplanted hMSC to bone regeneration. In conclusion, our data suggest that the application of autologous hMSC is superior to that of allogeneic cells for bone defect treatment.
Keyphrases
- bone marrow
- stem cell transplantation
- mesenchymal stem cells
- bone regeneration
- cell therapy
- bone mineral density
- hematopoietic stem cell
- endothelial cells
- high dose
- umbilical cord
- immune response
- induced apoptosis
- mouse model
- stem cells
- soft tissue
- bone loss
- platelet rich plasma
- transcription factor
- cell proliferation
- electronic health record
- dendritic cells
- cell cycle arrest
- low dose
- body composition
- endoplasmic reticulum stress
- oxidative stress
- inflammatory response
- replacement therapy
- long non coding rna