Pelled Gadi, Sheyn Dmitriy, Tawackoli Wafa, Jun Deuk Soo, Koh Youngdo, Su Susan, Cohn Yakubovich Doron, Kallai Ilan, Antebi Ben, Da Xiaoyu, Gazit Zulma, Bae Hyun, Gazit Dan
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.
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.
Stem Cells Int. 2016;2016:6530624. doi: 10.1155/2016/6530624. Epub 2015 Dec 7.
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.
因椎体压缩性骨折（VCF）而丧失能力的骨质疏松患者承受着沉重的经济和临床负担。目前的临床治疗侧重于症状管理，但并未从根源上解决问题。在这项初步研究中，将过表达BMP6基因的同种异体猪间充质干细胞（MSC-BMP6）悬浮于纤维蛋白凝胶中，并植入椎体缺损处，以在具有临床相关性的大型动物猪模型中研究其对骨再生的影响。为了检验BMP6修饰细胞对骨再生的作用，使用仅含纤维蛋白凝胶的构建体作为对照。在第6周和12周进行体内骨愈合评估，并在6个月时进行体外评估。体内CT显示，MSC-BMP6组在植入后6周内出现骨再生，而对照组的缺损部位仅见少量骨形成。6个月后，体外分析表明，与对照组相比，BMP6-MSC组的骨再生增强。这项临床前研究提出了一种创新的、可能微创的技术，该技术可用于利用同种异体基因修饰的间充质干细胞诱导骨再生，从而彻底改变目前对诸如骨质疏松相关椎体压缩性骨折等具有挑战性病症的治疗方法。
