Bakshi Ajay, Barshinger Alissa L, Swanger Sharon A, Madhavani Vinit, Shumsky Jed S, Neuhuber Birgit, Fischer Itzhak
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
J Neurotrauma. 2006 Jan;23(1):55-65. doi: 10.1089/neu.2006.23.55.
Cell transplantation as a treatment for spinal cord injury is a promising therapeutic strategy whose effective clinical application would be facilitated by non-invasive delivery protocols. Cells derived from the bone marrow are particularly attractive because they can be obtained easily, expanded to large numbers and potentially used for autologous as well as allogeneic transplantation. In this study we tested the feasibility of a novel minimally invasive method--lumbar puncture (LP)--for transplanting bone marrow stromal stem cells (MSC) into a clinically relevant spinal cord contusion model. We further sought to determine optimal protocols for performing such minimally invasive cell transplantation. Sprague-Dawley rats received a moderate contusion injury at the midthoracic level followed by LP transplantation of MSC derived from transgenic rats that express the human placental alkaline phosphatase (AP) reporter gene. The recipients were analyzed histologically to evaluate the extent of cell delivery and survival at the injury site. We found that MSC delivered by LP reached the contused spinal cord tissues and exerted a significant beneficial effect by reducing cyst and injury size. Transplantation within 14 days of injury provided significantly greater grafting efficiency than more delayed delivery, and increasing MSC dosage improved cell engraftment. The techniques described here can easily be translated to patients, thus accelerating clinical application of stem cell therapies.
细胞移植作为脊髓损伤的一种治疗方法，是一种很有前景的治疗策略，无创递送方案将有助于其在临床上的有效应用。源自骨髓的细胞特别有吸引力，因为它们易于获取、可大量扩增，并且有可能用于自体移植和异体移植。在本研究中，我们测试了一种新型微创方法——腰椎穿刺（LP）——将骨髓基质干细胞（MSC）移植到具有临床相关性的脊髓挫伤模型中的可行性。我们进一步试图确定进行这种微创细胞移植的最佳方案。将Sprague-Dawley大鼠在胸中段水平进行中度挫伤损伤，随后通过LP移植来自表达人胎盘碱性磷酸酶（AP）报告基因的转基因大鼠的MSC。对受体进行组织学分析，以评估损伤部位的细胞递送和存活程度。我们发现，通过LP递送的MSC到达了挫伤的脊髓组织，并通过减小囊肿和损伤大小发挥了显著的有益作用。损伤后14天内进行移植比更延迟的递送提供了显著更高的移植效率，并且增加MSC剂量可改善细胞植入。这里描述的技术可以很容易地转化应用于患者，从而加速干细胞疗法的临床应用。
