The Journal of Bone and Joint Surgery (American). 2008;90:1043-1052.
doi:10.2106/JBJS.G.00292
© 2008 The Journal of Bone and Joint Surgery, Inc.
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Stem Cells from Human Fat as Cellular Delivery Vehicles in an Athymic Rat Posterolateral Spine Fusion Model

Wellington K. Hsu, MD1, Jeffrey C. Wang, MD2, Nancy Q. Liu, PhD2, Lucie Krenek, MD2, Patricia A. Zuk, PhD3, Marc H. Hedrick, MD3, Prosper Benhaim, MD3 and Jay R. Lieberman, MD4

1 K4/703, 600 Highland Avenue, Box 7375 Clinical Science Center-H4, Madison, University of Wisconsin, WI 53792-3284. E-mail address: wkhsu{at}yahoo.com
2 Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California at Los Angeles, Center for Health Sciences 76-134, 10833 Le Conte Avenue, Los Angeles, CA 90095
3 Laboratory for Regenerative Bioengineering and Repair, Department of Surgery, David Geffen School of Medicine at University of California at Los Angeles, 7V-136 CHS, Los Angeles, CA 90095
4 Musculoskeletal Institute, Department of Orthopaedic Surgery, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-5456
Investigation performed at the Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the NIH, the American College of Surgeons, and DePuy. In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits in excess of $10,000 or a commitment or agreement to provide such benefits from a commercial entity (Cytori Therapeutics). No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Background: Mesenchymal stem cells derived from human liposuction aspirates, termed processed lipoaspirate cells, have been utilized as cellular delivery vehicles for the induction of bone formation in tissue engineering and gene therapy strategies. In this study, we sought to evaluate the efficacy of bone morphogenetic protein (BMP)-2-producing adipose-derived stem cells in inducing a posterolateral spine fusion in an athymic rat model.

Methods: Single-level (L4-L5) intertransverse spinal arthrodesis was attempted with use of a type-I collagen matrix in five groups of athymic rats, with eight animals in each group. Group I was treated with 5 x 106 adipose-derived stem cells transduced with an adenoviral vector containing the BMP-2 gene; group II, with 5 x 106 adipose-derived stem cells treated with osteogenic media and 1 µg/mL of recombinant BMP-2 (rhBMP-2); group III, with 10 µg of rhBMP-2; group IV, with 1 µg of rhBMP-2; and group V, with 5 x 106 adipose-derived stem cells alone. The animals that showed radiographic evidence of healing were killed four weeks after cell implantation and were examined with plain radiographs, manual palpation, microcomputed tomography scanning, and histological analysis.

Results: All eight animals in group I demonstrated successful spinal fusion, with a large fusion mass, four weeks postoperatively. Furthermore, group-I specimens consistently revealed spinal fusion at the cephalad level (L3 and L4), where no fusion bed had been prepared surgically. In contrast, despite substantial BMP-2 production measured in vitro, group-II animals demonstrated minimal bone formation even eight weeks after implantation. Of the groups treated with the application of rhBMP-2 alone, the one that received a relatively high dose (group III) had a higher rate of fusion (seen in all eight specimens) than the one that received the low dose (group IV, in which fusion was seen in four of the eight specimens). None of the group-V animals (treated with adipose-derived stem cells alone) demonstrated successful spine fusion eight weeks after the surgery.

Conclusions: Adipose-derived stem cells show promise as gene transduction targets for inducing bone formation to enhance spinal fusion in biologically stringent environments.

Clinical Relevance: Adipose-derived stem cells demonstrate potential as cellular vehicles for the delivery of recombinant protein in a regional gene therapy strategy to enhance spinal fusion. However, before the exclusive use of adipose-derived stem cells in a cell-based strategy can become routine, more extensive study of the biological potential, the interactions between different carriers, and the influence of host biology is necessary.


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