CD271 has been applied to isolate mesenchymal stem cells (MSCs) from bone marrow and other tissues. Umbilical cord blood is a unique resource of stem cells and endothelial progenitor cells. Isolation of MSCs from umbilical cord blood, however, has been inefficient and inconsistent. This study was designed to examine the potential application of CD271 as a marker for the isolation of MSCs from umbilical cord blood. CD271+ cells were isolated from umbilical cord blood and bone marrow using CD271 antibody-conjugated microbeads, and characterized in osteogenic, chondrogenic and adipogenic differentiation. CD271+ cells from umbilical cord blood were slow to proliferate compared with those isolated from bone marrow. While CD271+ cells from bone marrow differentiated into osteogenic, chondrogenic and adipogenic lineages, there were no sound indications of differentiation by CD271+ cells from umbilical cord blood under the same differentiation conditions applied to the CD271+ cells from bone marrow. The study also found that bone marrow CD271+ cells remarkably upregulated the expression of chondrogenic genes under chondrogenic differentiation induction. When implanted into bone defects in mice, CD271+ cells from bone marrow regenerated significant bone, but the counterparts in umbilical cord blood formed little bone in the bone defects. In conclusion, CD271 is an efficient marker for MSC isolation from bone marrow but has failed to isolate MSCs from umbilical cord blood. CD271+ cells in bone marrow are particularly chondrogenic. The property of CD271+ cells is unique but varies from different tissues.

These findings in a rat model suggest that the use of stem cells enhances healing after Achilles repair and that embedding of stem cells directly into suture offers sustained early benefit to tendon healing.

ObjectivesThe purpose of this study was to investigate the efficacy of a composite surgical mesh for delivery of mesenchymal stem cells (MSCs) in tendon repair.MethodsThe MSC-loaded mesh composed of a piece of conventional surgical mesh and a layer of scaffold, which supported MSC-embedded alginate gel. A 3-mm defect was surgically created at the Achilles tendon-gastrocnemius/soleus junction in 30 rats. The tendon defects were repaired with either 1) MSC-loaded mesh; or 2) surgical mesh only; or 3) routine surgical suture. Repaired tendons were harvested at days 6 and 14 for histology, which was scored on the bases of collagen organization, vascularity and cellularity, and immunohistochemisty of types I and III collagen.ResultsIn comparison with the other two repair types, at day 6, the MSC-loaded mesh significantly improved the quality of the repaired tendons with dense and parallel collagen bundles, reduced vascularity and increased type I collagen. At day 14, the MSC-loaded mesh repaired tendons had better collagen formation and organization.ConclusionThe MSC-loaded mesh enhanced early tendon healing, particularly the quality of collagen bundles. Application of the MSC-loaded mesh, as a new device and MSC delivery vehicle, may benefit to early functional recovery of the ruptured tendon.

Bone metastasis occurs frequently in renal cell carcinoma (RCC) patients causing significant morbidity by stimulating excessive osteolysis, yet the mechanisms responsible have been little studied. Matrix metalloproteinases (MMPs) are over-expressed in many cancer types and are believed to play a role in bone metastasis, however, the expression of MMPs in RCC bone metastasis (RBM) has not been investigated. Due to their ability to degrade the main component of organic bone matrix, type I collagen, we investigated the expression of MMP-1, -2, -8, -9, and -13 in RBM. By quantitative (q)RT-PCR, expression of MMP-13 was significantly increased in RBM tissues relative to that in RCC and adjacent normal kidney while no differences in the expression of MMP-1, -2, -8, or -9 mRNA were observed. Correspondingly, increased expression of MMP-13 protein was also observed in RBM relative to RCC by immunohistochemical analysis. Intriguingly, the expression of MMP-13 in the human RBM cell line RBM1-IT4 was stimulated by TGF-beta1, a growth factor abundant in the bone microenvironment and known to promote RBM-induced osteolysis in animals. Exposure of RBM1-IT4 cells to TGF-beta1 increased MMP-13 mRNA levels as well as the latent and active forms of MMP-13 protein. Further, stable expression of a dominant-negative TGF-beta type II receptor in RBM1-IT4 cells inhibited MMP-13 expression following TGF-beta1 exposure. These data suggest that MMP-13 expression is elevated in RBM relative to primary RCC and adjacent normal kidney, and is regulated at the cellular level by TGF-beta1.