BONE MARROW AS A SOURCE FOR PANCREATIC STEM CELLS

在胰腺损伤后观察到称为胰腺卵圆细胞的干细胞的独特表型的活化、增殖和分化。在某些生理条件下，卵圆细胞可以作为胰腺、导管、腺泡和胰岛细胞的不同类型上皮细胞的双能祖细胞。由于胰腺卵圆细胞和肝卵圆细胞在导致其激活的条件下具有惊人的相似性，因此有些人认为这些胰腺卵圆细胞和肝卵圆细胞是同一种细胞类型。肝卵圆细胞通常被认为是肝干细胞的后代，天然存在于肝脏。然而，最近，我们以及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，可以来自骨髓来源的前体细胞。也许，胰腺卵圆细胞，位于导管区域，并产生不同的上皮细胞类型，实际上可能来自胰腺外来源（即骨髓）。首先证明卵圆细胞可以从肝外来源获得，我们现在有技术通过使用性别不匹配的骨髓移植来回答细胞来源的问题。本项目的目标是鉴定和表型特征的骨髓相关细胞，可以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，旨在验证骨髓源性干细胞参与大鼠胰腺损伤后再生过程的假设。（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百分比的骨髓衍生胰腺细胞（特异性目的II）。我们有信心地预期，所提出的研究将产生关于胰腺卵圆细胞的总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胰腺再生的组织工程和细胞治疗技术干预提供有价值的资源。

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.