Rivas-Carrillo Jorge David, Okitsu Teru, Tanaka Noriaki, Kobayashi Naoya
Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Curr Med Chem. 2007;14(14):1573-8. doi: 10.2174/092986707780831096.
Embryonic stem (ES) cells may offer an unlimited cell source for the treatment of diabetes. However, a successful derivation of ES cells into islet-cells has proven to be more difficult than it was initially expected. Considering that the pancreas coordinates the global use of energy in the organism by secreting digestive enzymes and hormones, it is understandable that a sophisticated and tight regulation that lies on the pancreas itself to orchestrate its own tissue development and maturation. The complex process of endocrine cell differentiation can be better understood by analyzing the normal development of the pancreas. The proper detection of the signals provided in the pancreatic environment gives us a clue as to how the stem cells give rise to the whole pancreas. Careful and extensive screening of the natural or synthetic cytokines and growth factors and biochemical compounds that are essential in pancreatic development is required to properly mimic the process in vitro. Such a study would allow the researchers to achieve selective control of the differentiation and proliferation of the stem cells. The development and identification of the key molecules can provide us new insights into the pancreatic differentiation of the stem cells. We herein discuss the role of the microenvironment and transcriptional factors and cytokines, which have been recognized as important molecules during the major steps of the development of the pancreas. Finally, a more complete comprehension of the mechanisms that drive the pancreatic regeneration will provide us with new perspectives for future prophylactic and therapeutic interventions.
胚胎干细胞（ES细胞）可能为糖尿病治疗提供无限的细胞来源。然而，事实证明，将ES细胞成功诱导分化为胰岛细胞比最初预期的要困难得多。鉴于胰腺通过分泌消化酶和激素来协调机体能量的整体利用，胰腺自身存在复杂而严格的调控机制来协调其组织发育和成熟也就不足为奇了。通过分析胰腺的正常发育过程，可以更好地理解内分泌细胞分化的复杂过程。对胰腺环境中提供的信号进行恰当检测，能让我们了解干细胞如何发育成整个胰腺。为了在体外恰当地模拟这一过程，需要仔细而广泛地筛选胰腺发育中必不可少的天然或合成细胞因子、生长因子及生化化合物。这样的研究将使研究人员能够实现对干细胞分化和增殖的选择性控制。关键分子的发现和鉴定能够为我们深入了解干细胞向胰腺细胞的分化提供新的视角。我们在此讨论微环境、转录因子和细胞因子的作用，它们在胰腺发育的主要阶段已被确认为重要分子。最后，对驱动胰腺再生机制的更全面理解将为我们未来的预防和治疗干预提供新的视角。
