Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect.
BACKGROUND
Current cell therapy for cartilage regeneration requires invasive procedures, periosteal coverage and scaffold use. We have developed a novel transplantation method with synovial mesenchymal stem cells (MSCs) to adhere to the cartilage defect.


METHODS
For ex vivo analysis in rabbits, the cartilage defect was faced upward, filled with synovial MSC suspension, and held stationary for 2.5 to 15 minutes. The number of attached cells was examined. For in vivo analysis in rabbits, an autologous synovial MSC suspension was placed on the cartilage defect, and the position was maintained for 10 minutes to adhere the cells to the defect. For the control, either the same cell suspension was injected intra-articularly or the defects were left empty. The three groups were compared macroscopically and histologically. For ex vivo analysis in humans, in addition to the similar experiment in rabbits, the expression and effects of neutralizing antibodies for adhesion molecules were examined.


RESULTS
Ex vivo analysis in rabbits demonstrated that the number of attached cells increased in a time-dependent manner, and more than 60% of cells attached within 10 minutes. The in vivo study showed that a large number of transplanted synovial MSCs attached to the defect at 1 day, and the cartilage defect improved at 24 weeks. The histological score was consistently better than the scores of the two control groups (same cell suspension injected intra-articularly or defects left empty) at 4, 12, and 24 weeks. Ex vivo analysis in humans provided similar results to those in rabbits. Intercellular adhesion molecule 1-positive cells increased between 1 minute and 10 minutes, and neutralizing antibodies for intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and activated leukocyte-cell adhesion molecule inhibited the attachment.


CONCLUSIONS
Placing MSC suspension on the cartilage defect for 10 minutes resulted in adherence of >60% of synovial MSCs to the defect, and promoted cartilage regeneration. This adherent method makes it possible to adhere MSCs with low invasion, without periosteal coverage, and without a scaffold.
Koga
Hideyuki
H
Section of Orthopedic Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Shimaya
Masayuki
M
Muneta
Takeshi
T
Nimura
Akimoto
A
Morito
Toshiyuki
T
Hayashi
Masaya
M
Suzuki
Shiro
S
Ju
Young-Jin
YJ
Mochizuki
Tomoyuki
T
Sekiya
Ichiro
I
D000818:Animals; D002357:Cartilage Diseases / Q000473:pathology / Q000628:therapy*; D002448:Cell Adhesion; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007270:Injections, Intra-Articular; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000473:pathology / Q000628:therapy*; D011817:Rabbits; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors
D018799:Intercellular Adhesion Molecule-1