BONE MARROW AS A SOURCE FOR PANCREATIC STEM CELLS

胰腺损伤后，观察到一种不同表型的干细胞，称为胰腺卵圆细胞的激活、增殖和分化。在一定的生理条件下，卵形细胞可作为胰腺不同类型上皮细胞、导管细胞、腺泡细胞和胰岛细胞的双电位祖细胞。由于胰腺卵圆细胞和肝卵圆细胞在激活条件上有着惊人的相似之处，一些人认为胰腺卵圆细胞和肝卵圆细胞属于同一细胞类型。肝卵圆细胞通常被认为是肝干细胞的后代，原产于肝脏。然而，最近，我们和其他人已经获得了明确的证据，在大鼠肝卵圆细胞，或至少其中的一部分，可以来自骨髓起源的前体细胞。也许，位于导管区并产生不同上皮细胞类型的胰腺卵圆形细胞实际上可能来源于胰腺外来源（即骨髓）。作为第一个证明卵形细胞可以从肝外来源获得的人，我们现在有了通过使用性别不匹配的骨髓移植来回答细胞起源问题的技术。本项目的目标是鉴定骨髓相关细胞并对其进行表型表征，该细胞可作为胰腺卵圆细胞的祖细胞。为了实现这些目标，我们将进行一系列的研究，旨在验证骨髓干细胞参与损伤大鼠胰腺再生过程的假设。（具体目标一）；并确定骨髓细胞的CD-34 +或CD-34-亚群是否含有卵圆细胞祖细胞并产生最高比例的骨髓衍生胰腺细胞（Specific Aim II）。我们可以满怀信心地预测，所提出的研究将产生关于胰腺卵圆细胞整体生物学及其骨髓前体的基本表型和特性的新的重要数据。同样的数据可能为未来组织工程和细胞治疗技术干预胰腺再生提供有价值的资源。

Activation, proliferation and differentiation of a distinct phenotype of stem cells, called pancreatic oval cells, are observed after pancreatic injuries. Under certain physiological conditions, oval cells can act as bipotential progenitors of the different types of epithelial cells of the pancreas, the ducts, acinar and islet cells. Because pancreatic oval cells and hepatic oval cells share an uncanny number of similarities in the conditions that cause their activation, some have considered these pancreatic and hepatic oval cells to be one in the same cell type. The hepatic oval cells have been usually thought to be the progeny of a hepatic stem cell, native to the liver. Recently, however, we as well as others have obtained clear evidence that in the rat hepatic oval cells, or at least a fraction of them, can be derive from a precursor cell of bone marrow origin. Perhaps, the pancreatic oval cells, which lie in the ductular region and gives rise to the different epithelial cell types may in fact be derived from an extra-pancreatic source (i.e. bone marrow). Having been the first to show that oval cells can be derived from an extra-hepatic source we now have the technology to answer the question of cell of origin through the use of sex mismatched bone marrow transplants. The goals of this project are to identify and phenotypically characterize the bone marrow-associated cell that can act as a progenitor of pancreatic oval cells. Towards achievement of these goals, we will perform a series of studies aimed at to test the hypothesis that bone marrow derived stem cells participate in the regeneration process in the injured rat pancreas. (Specific Aim I); and to establish whether the CD- 34+ or CD-34- sub-population of bone marrow cells contains the oval cell progenitor and produces the highest percentage of bone marrow derived pancreatic cells (Specific Aim II). It is anticipated, with confidence, that performance of the proposed studies will yield new and significant data about the overall biology of pancreatic oval cells, and the basic phenotype and properties of their bone marrow precursor. The same data could potentially provide a valuable resource for future tissue engineering and cell therapy technique interventions in pancreatic regeneration.