Cartilage repair using bone morphogenetic protein 4 and muscle‐derived stem cells

Wiley - Tập 54 Số 2 - Trang 433-442 - 2006
Ryosuke Kuroda1, Arvydas Ūsas2, Seiji Kubo2, Karin A. Corsi2, Hairong Peng2, Tim Rose2, James H. Cummins3, Freddie H. Fu4, Johnny Huard2
1Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
2Children's Hospital of Pittsburgh, and University of Pittsburgh, Pittsburgh, Pennsylvania
3Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
4University of Pittsburgh, Pittsburgh, Pennsylvania

Tóm tắt

AbstractObjectiveMuscle‐derived stem cells (MDSCs) isolated from mouse skeletal muscle exhibit long‐time proliferation, high self‐renewal, and multipotent differentiation. This study was undertaken to investigate the ability of MDSCs that were retrovirally transduced to express bone morphogenetic protein 4 (BMP‐4) to differentiate into chondrocytes in vitro and in vivo and enhance articular cartilage repair.MethodsUsing monolayer and micromass pellet culture systems, we evaluated the in vitro chondrogenic differentiation of LacZ‐ and BMP‐4–transduced MDSCs with or without transforming growth factor β1 (TGFβ1) stimulation. We used a nude rat model of a full‐thickness articular cartilage defect to assess the duration of LacZ transgene expression and evaluate the ability of transplanted cells to acquire a chondrocytic phenotype. We evaluated cartilage repair macroscopically and histologically 4, 8, 12, and 24 weeks after surgery, and performed histologic grading of the repaired tissues.ResultsBMP‐4–expressing MDSCs acquired a chondrocytic phenotype in vitro more effectively than did MDSCs expressing only LacZ; the addition of TGFβ1 did not alter chondrogenic differentiation of the BMP‐4–transduced MDSCs. LacZ expression within the repaired tissue continued for up to 12 weeks. Four weeks after surgery, we detected donor cells that coexpressed β‐galactosidase and type II collagen. Histologic scoring of the defect sites 24 weeks after transplantation revealed significantly better cartilage repair in animals that received BMP‐4–transduced MDSCs than in those that received MDSCs expressing only LacZ.ConclusionLocal delivery of BMP‐4 by genetically engineered MDSCs enhanced chondrogenesis and significantly improved articular cartilage repair in rats.

Từ khóa


Tài liệu tham khảo

10.1016/S0749-8063(96)90179-6

10.1177/03635465980260022701

10.1016/S0889-857X(21)00341-0

10.1016/S0749-8063(86)80012-3

10.3928/0147-7447-19970601-08

10.1056/NEJM199410063311401

10.1002/jor.1100070208

10.1007/PL00021232

10.1016/0142-9612(96)85759-0

10.2106/00004623-198567060-00013

10.1016/0749-8063(95)90065-9

10.3109/17453679008993062

10.1016/S0749-8063(05)80428-1

10.1126/science.284.5411.143

10.1016/0014-5793(96)00240-2

Adachi N, 2002, Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects, J Rheumatol, 29, 1920

10.1083/jcb.200108150

10.1038/ncb1008

10.1038/43919

10.1083/jcb.150.5.1085

10.1016/S0006-291X(88)80887-8

10.1002/art.10759

10.1002/art.1780400605

10.1111/j.1432-1033.1990.tb15595.x

Morales TI, 1988, Transforming growth factor β regulates the metabolism of proteoglycans in bovine cartilage organ cultures, J Biol Chem, 263, 12828, 10.1016/S0021-9258(18)37634-8

10.1016/0014-5793(88)81327-9

10.2106/00004623-199710000-00002

10.1042/bj2600543

10.1002/(SICI)1097-0177(200004)217:4<401::AID-DVDY7>3.0.CO;2-D

10.1016/S0925-4773(99)00339-1

10.1016/S0736-0266(03)00100-1

10.1084/jem.171.1.231

10.1006/mthe.2001.0423

10.1172/JCI15153

10.1006/excr.1997.3858

10.2106/00004623-198870040-00017

10.1016/j.bone.2004.01.028

10.1242/jcs.00527

10.1016/j.bbrc.2004.06.029

10.1016/S0040-8166(02)00106-4

10.2106/00004623-199812000-00004

10.1089/ten.1998.4.415

10.1006/excr.2001.5278

10.1097/00003086-200110001-00019

10.1053/joca.2002.0869

10.1002/jcb.20019

10.1016/S1063-4584(97)80023-4

10.1016/S1063-4584(97)80007-6

10.3109/17453679308993663

10.1083/jcb.105.3.1443

Thông tin
Thông tin xuất bản

Wiley

Tập 54 Số 2

433-442

Thông tin tác giả