Fig 3. Connective tissue repair by MSCs.

A, B: Orthotopic bone repair

Segmental critical size bone defect (2 mm) created in femoral midshaft of athymic nude mice; the defect was filled with MSC-ceramic transplant.

A: Defect in the absence of grafting; note the presence of fibrous tissue filling the gap

B: Bone reconstruction (8 weeks after engraftment) was apparent in place of the fibrous tissue (arrow).

C, D: Orthotopic cartilage repair

Large size defect was created in the patella of Merinos sheep. Autologous bone marrow MSCs were harvested and expanded in culture for 2 passages, before being seeded in fibrin clots or scaffolds of chitosan + TGFb3. The material was implanted in the patella defect. Animals were left in the field for 8 weeks before sacrifice.

C: lesions filled with ovine MSC in fibrin clot

D: Lesions filled with ovine MSCs embedded in chitosan scaffolds + TGFβ3. Arrows indicate the junction between endogenous and new tissues

E: Heterotopic tendon formation

The intramuscular transplantation of adenovirally modified MSCs (C3H10T½ embryonic cell line) expressing Smad8 and Bmp2 leads, 4 weeks after implantation, to the heterotopic formation of tendinous elements (hematoxylin and eosin staining). The tendinous element (shown within the black and white arrowheads) is characterized by a tendon-typical crimp pattern and flattened tenocyte-like cells. Abbreviations: B, bone; M, muscle; T, tendon