Bone-derived Mesenchymal Stem Cells Research Articles

In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection

Objective To track superparamagnetic iron oxide nanoparticle (SPIO)-labeled, bone-derived mesenchymal stem cells (MSCs) by in vivo magnetic resonance imaging (MRI) with a 1.5 T-system following injection of engineered autologous MSCs into the knee joint cavity in rabbit articular cartilage defect models. Methods Rabbit MSCs were labeled with SPIO and a transfection agent. Cell viability, proliferation and differentiation capacity were assessed in vitro using appropriate functional assays. Cells underwent GRE T2*-weighted MRI in vitro. The autologous MSCs seeded in chitosan and glycerophosphate (C-GP) gel were injected into the knee joint cavity of rabbit models for cartilage defects. All rabbits underwent GRE T2*-weighted MRI 1, 4, 8 and 12 weeks post-injection. MR imaging findings were compared histologically. Results Nanoparticles were stained with Prussian blue and observed by transmission electron microscopy inside the cells. Cell viability, proliferation, and differentiation were comparable between labeled and non-labeled cells. After intra-articular injection of labeled autologous MSCs, marked hypointense signal void areas representing the injected MSCs can be observed for at least 12 weeks on GRE T2*-weighted images. At 12 weeks post-injection, labeled MSCs migrated into the synovial fluid at the suprapatellar bursa, the popliteal space site and subchondral bone of the femur but no MSCs were detected in the defect. Histochemical staining confirmed the presence of Prussian blue-positive cells and BrdU-positive cells. Conclusions MRI would be an efficient noninvasive technique to visually track SPIO-labeled seed cells in vivo; the engineered autologous MSCs do not actively participate in the repair of articular cartilage defects following intra-articular injection.

Treatment of type 1 diabetes by transplantation of bone-derived mesenchymal stem cells expressing human insulin gene: experiment with mice

To evaluate the effect of treatment of type 1 diabetes by transplantation of bone-derived stem cells expressing human insulin gene. Murine bone marrow-derived stem cells expressing green fluorescent protein (GFP-mMSCs) were isolated from 4/6-week-old GFP mice and transfected with a recombinant retrovirus-murine stem cell virus (MSCV) encoding human insulin gene, thus constructing the GFP-mMSCs-MCV-insulin. 16 C57BL/6J mice were injected with streptozotocin so as to establish models of type 1 diabetes and then randomly divided into 4 equal groups: Group A, undergoing injection into the liver with GFP-mMSC-MCV-insulin 1 week after the establishment of the model, Group B, undergoing intrahepatic transplantation of the GFP-mMSCs transfected with blank vector, Group C, undergoing intrahepatic transplantation of untransfected GFP-mMSCs, and Group D, undergoing intrahepatic transplantation of phosphate-buffered saline (PBS). Another 4 normal mice were used as controls and underwent intrahepatic transplantation of PBS too. After the transplantation the blood glucose, serum insulin, and body weight were detected everyday. 6 weeks later immunohistochemistry was used to detect the expression of human insulin in the mice liver tissues. The body weight of Group A increased by 6% within 6 weeks after treatment, and the average blood glucose level 7 d and 42 d after transplantation were (10.4 +/- 2.8) mmol/L and (6.5 +/- 0.9) mmol/L respectively, both significantly lower than those of Group D [(26.8 +/- 2.5) mmol/L and (25.4 +/- 4.1) mmol/L respectively, both P < 0.05]. Immunohistochemistry showed secretion of human insulin in serum and liver. The clinical manifestations of diabetes can be relieved effectively by intrahepatic transplantation of mMSCs expressing human insulin gene. This study implies a novel approach of gene therapy for type 1 diabetes.

Repair of Major Cuff Ruptures

The rotator cuff (RC) repair failure rate is high. Tendon and bone represent sources of mesenchymal stem cells (MSCs), but the number of MSCs from each has not been compared. Bone channeling may increase bone-derived MSC numbers participating in enthesis re-formation at the “footprint” repair site. The effect of preoperative channeling on increasing bone MSC numbers has never been reported. We asked (1) whether bone contains more MSCs than tendon at the time of arthroscopic repair and (2) whether bone preoperative channeling at the RC repair site increases the number of bone-derived MSCs at the time of surgery.In 23 participants undergoing arthroscopic RC repair, bone was sampled from the footprint and tendon was sampled from the distal supraspinatus. We randomized participants to the channeling or no-channeling group 5 to 7 days before surgery. We enumerated MSCs from both tissues using the colony-forming unit–fibroblast (CFU-F) assay (10 per group). We identified MSC identity using flow cytometry and MSC tri-differentiation capacity (n = 3).Tendon CFU-F per gram exceeded bone CFU-F per gram for both groups (479 ± 173 CFU-F/g vs. 162 ± 54 CFU-F/g for channeling [P = .036] and 1334 ± 393 CFU-F/g vs. 284 ± 88 CFU-F/g for no channeling [P = .009]). Ninety-nine percent of cultured cells satisfied the MSC definition criteria.The distal supraspinatus tendon contained more MSCs per gram than the humeral footprint. Tendon may represent an important and overlooked MSC source for postoperative enthesis re-formation. Further studies are needed to evaluate the repair role of tendon MSCs and to recommend bone channeling in RC repair.