title: BMP6-Engineered MSCs Induce Vertebral Bone Repair in a Pig Model: A Pilot Study.
abstract: Osteoporotic patients, incapacitated due to vertebral compression fractures (VCF), suffer grave financial and clinical burden. Current clinical treatments focus on symptoms' management but do not combat the issue at the source. In this pilot study, allogeneic, porcine mesenchymal stem cells, overexpressing the BMP6 gene (MSC-BMP6), were suspended in fibrin gel and implanted into a vertebral defect to investigate their effect on bone regeneration in a clinically relevant, large animal pig model. To check the effect of the BMP6-modified cells on bone regeneration, a fibrin gel only construct was used for comparison. Bone healing was evaluated in vivo at 6 and 12 weeks and ex vivo at 6 months. In vivo CT showed bone regeneration within 6 weeks of implantation in the MSC-BMP6 group while only minor bone formation was seen in the defect site of the control group. After 6 months, ex vivo analysis demonstrated enhanced bone regeneration in the BMP6-MSC group, as compared to control. This preclinical study presents an innovative, potentially minimally invasive, technique that can be used to induce bone regeneration using allogeneic gene modified MSCs and therefore revolutionize current treatment of challenging conditions, such as osteoporosis-related VCFs.
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Skeletal Biotech Laboratory, Hadassah Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Sheyn
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Wafa
authors.initials: W
authors.lastname: Tawackoli
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Orthopaedic Surgery, Gil Medical Center, Gachon University of Medicine & Science, Incheon, Republic of Korea.
authors.forename: Deuk Soo
authors.initials: DS
authors.lastname: Jun
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Orthopedics, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Youngdo
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Su
authors.affiliation: Skeletal Biotech Laboratory, Hadassah Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Cohn Yakubovich
authors.affiliation: Skeletal Biotech Laboratory, Hadassah Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Kallai
authors.affiliation: Skeletal Biotech Laboratory, Hadassah Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel; US Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX 78234, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Antebi
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Da
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Skeletal Biotech Laboratory, Hadassah Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Zulma
authors.initials: Z
authors.lastname: Gazit
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Hyun
authors.initials: H
authors.lastname: Bae
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Skeletal Biotech Laboratory, Hadassah Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit