BONE MARROW AS A SOURCE FOR PANCREATIC STEM CELLS

胰腺损伤后，可以观察到一种不同表型的干细胞，即胰腺卵圆细胞的激活、增殖和分化。在一定的生理条件下，卵圆细胞可以作为不同类型的胰腺上皮细胞、导管、腺泡和胰岛细胞的双潜祖细胞。由于胰腺卵圆细胞和肝卵圆细胞在导致其激活的条件上有惊人的相似之处，一些人认为这些胰腺卵圆细胞和肝卵圆细胞是同一类型的细胞。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，我们和其他人获得了明确的证据，在大鼠的肝脏中，卵圆细胞，或者至少是其中的一部分，可以来自骨髓起源的前体细胞。也许，位于胰管区的胰腺卵圆细胞产生了不同的上皮细胞类型，实际上可能来自胰腺外的来源(即骨髓)。由于首次证明卵圆细胞可以来自肝外来源，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。该项目的目标是鉴定和表型鉴定可作为胰腺卵圆细胞祖细胞的骨髓相关细胞。为了实现这些目标，我们将进行一系列研究，旨在验证骨髓源干细胞参与损伤大鼠胰腺再生过程的假设。(特定目标I)；以及确定CD-34+或CD-34-亚群的骨髓细胞是否含有卵圆细胞祖细胞并产生最高比例的骨髓来源的胰腺细胞(特定目标II)。充满信心地预计，拟议研究的执行将产生关于胰腺卵圆细胞的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。同样的数据可能会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.