Treatment of Osteoradionecrosis with Bone Marrow Stromal Cells

骨髓基质细胞治疗放射性骨坏死

基本信息

批准号：
7893103
负责人：
Sunday O Akintoye
金额：
$ 13.84万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
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/7893103
关键词：
Affect Anatomy Animal Experimentation Animals Autologous Bone Marrow Bone Regeneration Bone Transplantation Cell Culture Techniques Cell Proliferation Cells Cherubism Clinical Clinical Data Clinical Protocols Complication Data Defect Deformity Dental Schools Dentistry Disease Excision Face Goals Head Head and Neck Cancer Healed Hematopoiesis Hematopoietic Human Hyperbaric Oxygenation Immunocompromised Host In Vitro Infection Jaw Mandible Medicine Mentorship Mesoderm Methods Modality Mus Natural regeneration Neural Crest Neural Crest Cell Nude Rats Operative Surgical Procedures Osteogenesis Osteoradionecrosis Pathogenesis Patients Pelvis Pennsylvania Property Quality of life Radiation Radiation Tolerance Radiation-Induced Change Radio Research Resistance Role Saturn&apos s Moon Phoebe Scientist Site Sternum Stromal Cells Study Section Survivors Syndrome Technology Testing Tissue Engineering Tissues Training Translating Translational Research Transplantation Trauma Universities base bone bone marrow stromal stem cell cancer radiation therapy career clavicle craniofacial face bone structure healing ilium improved in vivo insight irradiation long bone mandible/maxilla maxillofacial osteogenic reconstruction regenerative repaired rib bone structure skeletal social stigma tibia tissue oxygenation translational study tumor volunteer

项目摘要

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.

描述（由申请人提供）：Akintoye 博士对牙科研究和学术的承诺为他在宾夕法尼亚大学牙科医学院担任独立临床医生科学家做好了准备。这个K08应用程序是在博士的指导下进行的。 Phoebe Leboy 和 Marjorie Jeffcoat 致力于应用骨髓基质细胞 (BMSC) 技术来治疗放射性骨坏死并提供转化研究培训。在口面部区域，放射性骨坏死是头颈癌放射治疗的主要并发症，其特征是组织裂开、骨骼暴露、面部畸形、口面部功能受损和生活质量下降。目前放射性骨坏死的非手术治疗是高压氧疗法，可暂时改善组织氧合。结果各不相同，因为愈合不完全，对某些患者来说是禁忌的，并且通常需要随后手术切除受影响的骨头。临床数据表明，用轴骨自体移植来桥接颌骨骨缺损的颌面重建经常会导致不整合和移植物再吸收，而从其他口面部部位移植骨通常更成功。同样，诸如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，从未在其他网站中被描述过。颌骨独特的这些特性仍不清楚，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）的不同胚胎学起源有关，但人类骨髓间充质干细胞的解剖骨骼位点特异性特性尚未最终确定。使用来自不同骨骼部位的离体扩增的骨髓间充质干细胞移植来再生放射性坏死骨中的新骨也尚未在人类或动物中进行过探索。 Akintoye 博士在第一个具体目标中提出研究上颌骨和下颌骨（神经嵴起源）和髂骨（中胚层起源）的人类 BMSC 的特定位点独特的成骨特性和放射敏感性。第二个具体目标是阐明人类 BMSC 在无胸腺大鼠自发性放射性骨坏死中的位点特异性再生特性。通过移植来自下颌骨和髂嵴的正常人骨髓间充质干细胞，他将研究并比较它们作为移植物治疗放射性骨坏死的功效。需要新的方法来治疗骨缺损；我们建议使用组织工程技术（体外扩增的 BMSC）来治疗放射性骨坏死，这是一种与头颈癌放疗相关的顽固性临床问题。这些数据将提供大量新见解。 Akintoye 博士的长期目标是最终将这些转化为治疗放射性骨坏死患者的人类临床方案。