Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK

<p>Abstract</p> <p>Background</p> <p>Islet transplantation provides a promising cure for Type 1 diabetes; however it is limited by a shortage of pancreas donors. Bone marrow-derived multipotent mesenchymal stem cells (MSCs) offer renewable cells for generating insulin-producing cells (IPCs).</p> <p>Methods</p> <p>We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation.</p> <p>Results</p> <p>Here, we report adding extracellular matrix proteins (ECM) such as fibronectin (FN) or laminin (LAM) enhances pancreatic differentiation with increases in insulin and Glut2 gene expressions, proinsulin and insulin protein levels, and insulin release in response to elevated glucose concentration. Adding FN or LAM induced activation of Akt and ERK. Blocking Akt or ERK by adding LY294002 (PI3K specific inhibitor), PD98059 (MEK specific inhibitor) or knocking down Akt or ERK failed to abrogate FN or LAM-induced enhancement of IPC differentiation. Only blocking both of Akt and ERK or knocking down Akt and ERK inhibited the enhancement of IPC differentiation by adding ECM.</p> <p>Conclusions</p> <p>These data prove IPC differentiation by MSCs can be modulated by adding ECM, and these stimulatory effects were mediated through activation of Akt and ERK pathways.</p

Collagen-Hydroxyapatite Microspheres as Carriers for Bone Morphogenic Protein-4

The purpose of the current study is to evaluate the carrier capability of collagen-hydroxyapatite microspheres to the bone morphogenic proteins ( BMP). After anesthesia, a bone defect (6.0 mm in diameter and 10.0 mm in depth) was created at the distal femoral condyles of New Zealand white rabbits . These 10.0 mm(3) defects were then completely filled with the implant materials. After 2, 4, 6, and 8 weeks, the animals were sacrificed and histological evaluations were performed. The results showed that when the defects were left untreated, there was no evidence of bone formation during the eight-week experimental period. In the group treated with collagen-hydroxyapatite microspheres without BMP-4, the defect was filled with fibrous tissue and inflammatory cells, while active bone formation with mature marrow tissue formation was evident in the defect treated with collagen-hydroxyapatite microspheres containing BMP-4. Collagen- hydroxyapatite microspheres were expected to be replaced by the regenerated bone structure as the bone reconstruction and bone remodelling process occurred. It was apparent that bone regeneration was influenced by the addition of BMP-4. Collagen-hydroxyapatite microspheres were good carriers for bone morphogenic proteins