Treatment of Osteoradionecrosis with Bone Marrow Stromal Cells

骨髓基质细胞治疗放射性骨坏死

• 批准号: 7084879
• 负责人: Sunday O Akintoye
• 金额: $ 13.83万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7084879
• 关键词: bone; bone marrow; clinical research; human; stromal cells

DESCRIPTION (provided by applicant): Dr. Akintoye's commitment to research and academic dentistry have prepared him for a career as an independent Clinician-Scientist at the School of Dental Medicine, University of Pennsylvania. This K08 application, under the mentorship of Drs. Phoebe Leboy and Marjorie Jeffcoat, seeks to apply bone marrow stromal cell (BMSC) technology to treat osteoradionecrosis and provide training in translational research. In the oro-facial region, osteoradionecrosis is a major complication of head and neck cancer radiotherapy characterized by tissue dehiscence, bone exposure, facial deformities, compromised oro-facial function and diminished quality of life. Current non-surgical treatment of osteoradionecrosis is hyperbaric oxygen therapy that improves tissue oxygenation transiently. The results are variable as healing is incomplete, it is contra-indicated in some patients and subsequent surgical resection of affected bones is often needed. Clinical data indicate that maxillofacial reconstruction with autologous graft from the axial bones to bridge osseous jaw defects often results in non-integration and graft resorbtion, while grafting bone from other oro-facial sites is usually more successful. Similarly, diseases such as cherubism and hyperparathyroid jaw tumor syndrome are restricted to the jaw bones and never been described in other sites. These properties unique to the jaw bones still remain unclear and need to be further elucidated. They may be related to the different embryological origins of the craniofacial (neural crest origin) and axial (mesodermal origin) bones, but anatomic skeletal site-specific properties of human BMSC have not been conclusively defined. Regeneration of new bone in radionecrotic bone using grafted ex vivo expanded BMSC from different skeletal sites has also not been explored either in humans or animals. Dr. Akintoye has proposed in the first specific aim to investigate site-specific distinctive osteogenic properties and radiosensitivity of human BMSC of the maxilla and mandible (neural crest origin) and ilium (mesodermal origin). The second specific aim will elucidate site-specific regenerative properties of human BMSC in spontaneous osteoradionecrosis in athymic rats. By transplanting normal human BMSC from mandible and iliac crest, he will study and compare their efficacy as graft to heal osteoradionecrosis. New methods are needed to treat osseous defects; we propose the use of tissue engineering technology (ex vivo expanded BMSC) to treat osteoradionecrosis, a recalcitrant clinical problem associated with head and neck cancer radiotherapy. These data will provide substantial new insights. Dr. Akintoye's long term goal is to ultimately translate these into human clinical protocols to treat patients with osteoradionecrosis.

简介（由申请人提供）：Akintoye博士致力于研究和学术牙科，为他在宾夕法尼亚大学牙科医学院作为独立临床医生和科学家的职业生涯做好了准备。本次K08应用，在博士的指导下。菲比·莱博伊和马乔里·杰弗里特，寻求应用骨髓基质细胞（BMSC）技术治疗骨放射性坏死，并提供转化研究方面的培训。在口腔-面部区域，骨放射性坏死是头颈癌放疗的主要并发症，其特征是组织开裂、骨暴露、面部畸形、口腔-面部功能受损和生活质量下降。目前骨放射性坏死的非手术治疗是高压氧治疗，它能短暂地改善组织氧合。由于愈合不完全，结果是可变的，在一些患者中是禁忌的，随后通常需要手术切除受影响的骨骼。临床资料表明，骨轴骨自体移植物修复颌面骨缺损往往导致骨不整合和移植物吸收，而其他部位的骨移植通常更成功。同样，诸如小天使病和甲状旁腺功能亢进颌骨肿瘤综合征等疾病仅限于颌骨，从未在其他部位被描述过。这些颌骨特有的特性仍然不清楚，需要进一步阐明。它们可能与颅面骨（神经嵴起源）和轴骨（中胚层起源）的不同胚胎起源有关，但人类骨髓间质干细胞的解剖骨骼部位特异性尚未得到明确定义。利用从不同骨骼部位移植的体外扩展骨髓间充质干细胞在放射性坏死骨中再生新骨也尚未在人类或动物中进行过探索。Akintoye博士提出的第一个具体目标是研究人类上颌骨和下颌骨（神经嵴起源）和髂骨（中胚层起源）的BMSC的部位特异性独特成骨特性和放射敏感性。第二个具体目标是阐明人类骨髓间充质干细胞在无胸大鼠自发性放射性骨坏死中的部位特异性再生特性。他将通过从下颌骨和髂骨移植正常人骨髓间充质干细胞，研究并比较其作为移植物治疗放射性骨坏死的疗效。治疗骨缺损需要新的方法；我们建议使用组织工程技术（体外扩展BMSC）来治疗与头颈癌放疗相关的顽固性临床问题-骨放射性坏死。这些数据将提供实质性的新见解。Akintoye博士的长期目标是最终将这些转化为人类临床方案，以治疗骨放射性坏死患者。