OLD AGE AND INDUCIBLE OSTEOGENIC PRECURSOR CELLS

老年和可诱导的成骨前体细胞

• 批准号: 2546681
• 负责人: ARNOLD KAHN
• 金额: $ 1.95万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2546681
• 关键词: cell age; guinea pigs; laboratory mouse; osteoblasts; osteogenesis

Bone formation (matrix synthesis) is the product of osteoblasts most immediately recruited and differentiated from stem cell populations located in the stromal compartment of bone marrow and in the periosteum. However, these are not the only stem cells with osteogenic developmental potential. Other stem cells which have the capacity form bone and cartilage are located in connective tissue in multiple parts of the body (e.g., muscle, spleen and thymus) and will undergo osteogenic differentiation upon exposure to an osteo-inductive agent. The physiological role of these inducible osteogenic precursor cells (IOPCs) is still a matter of speculation but one possibility is that they are part of a circulating pool of multipotential stem cells that may take up residence in marrow and contribute to osteogenesis in bone. It is now reasonably well established that the stem cell population located in the bone marrow stroma (determined osteogenic precursor cells; DOPCs) undergoes a marked age-related reduction in number and osteogenic potential, and it is likely that this reduction contributes to the decline in the level bone formation associated with Type II ("senile") osteoporosis. No such information on possible population change exists for IOPCs. In the present application, we propose to make this determination in young and old mice and guinea pigs using in vitro and in vivo methods established by the foreign collaborator, Prof. A. Friedenstein, for isolating, culturing and assessing the osteogenic potential of IOPCs derived from spleen and thymus. Specifically, we will determine (1) whether the spleen and thymus of old mice and guinea pigs contain fewer of the clonogenic precursor cells (CFU-f) and IOPCs than young animals, (2) whether explanted older animal IOPCs have reduced osteogenic potential and (3) whether there is a reduction in the capacity of older animals to respond to osteoinductive stimulation in situ. Should the latter be observed, it would provide indirect but important confirmation of lowered IOPC numbers and/or developmental potential in old animals.

骨形成(基质合成)主要是成骨细胞的产物 立即从干细胞群体中招募和分化 位于骨髓间质室和骨膜中。 然而，这些并不是唯一具有成骨发育的干细胞。 潜力。其他有能力的干细胞形成骨骼和 软骨位于身体多个部位的结缔组织中。 (例如肌肉、脾和胸腺)，并将进行成骨 暴露于骨诱导剂后的分化。这个 这些可诱导成骨前体细胞的生理作用 仍然是一个猜测的问题，但有一种可能性是，它们是 循环中的多潜能干细胞池可能会占据 滞留在骨髓中，有助于骨中的成骨。现在是时候了 合理地确定了干细胞种群位于 骨髓基质(已确定的成骨前体细胞；DOPC) 与年龄相关的数量和成骨能力显著减少 潜力，而这种减少很可能是导致下降的原因 在与II型相关的水平骨形成(“老年性”) 骨质疏松。不存在关于可能的人口变化的此类信息 IOPC。在本申请中，我们建议做出这一确定 在小鼠、老年小鼠和豚鼠身上使用体外和体内方法 由外国合作者A.Friedenstein教授为 人工晶状体上皮细胞的分离、培养及成骨能力评价 来源于脾和胸腺。具体来说，我们将确定(1) 老年小鼠和豚鼠的脾和胸腺是否含有较少的 幼年动物的克隆性前体细胞(CFU-f)和IOPC，(2) 移植的老年动物IOPC是否降低了成骨潜力 (3)年龄较大的动物是否有能力减少 对原位骨诱导刺激有反应。应该是后者吗？ 观察到，它将提供间接但重要的确认 老年动物的IOPC数量和/或发育潜力。