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: 7668426
• 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/7668426
• 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' 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

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博士对研究和学术牙科的承诺为他在宾夕法尼亚大学牙科医学院担任独立的临床科学家做好了准备。在Phoebe Leboy和Marjorie Jeffcoat博士的指导下，K08申请旨在应用骨髓基质细胞（BMSC）技术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，其特征在于组织裂开、骨暴露、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治疗，可短暂改善组织氧合。结果是可变的，因为愈合不完全，它是禁忌在一些患者和随后的手术切除受影响的骨头往往是必要的。临床资料表明，自体中轴骨移植修复颌骨缺损，往往导致骨不连和骨吸收，而从其他口面部部位移植骨通常更成功。类似地，像巨像症和甲状旁腺增生性颌骨肿瘤综合征这样的疾病仅限于颌骨，从未在其他部位描述过。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（神经嵴起源）和中轴（中胚层起源）骨的不同胚胎学起源有关，但人类BMSC的解剖骨骼部位特异性特性尚未最终确定。使用来自不同骨骼部位的移植的离体扩增的BMSC在放射性坏死的骨中再生新骨也尚未在人或动物中探索。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BMSC的部位特异性独特成骨特性和放射敏感性。第二个具体的目标将阐明在自发性骨放射性坏死在无胸腺大鼠的人BMSC的网站特定的再生性能。他将研究和比较从下颌骨和髂嵴移植的正常人骨髓间充质干细胞作为移植物治疗放射性骨坏死的疗效。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，这是一个与头颈癌放射治疗相关的棘手的临床问题。这些数据将提供大量新的见解。Akintoye博士的长期目标是最终将这些转化为人类临床方案，以治疗放射性骨坏死患者。