ABSTRACT
Blood transfusion is a vital part of the treatment offered patients with fatal anemia and thrombocytopenia. However, the declining population of blood donors and the increasing risk of viral infection make an alternative transfusion system, one that is not dependent on donor blood, highly desirable. In this context, a number of different alternative sources of megakaryocytes have been suggested, including hematopoietic stem cells (HSCs) from bone marrow (Debili et al. 1995), cord blood (Matsunaga et al. 2006; Schipper et al. 2003) or adipose tissue (Matsubara et al. 2009). But it has proven diffi cult to generate megakaryocytes and platelets on a large scale, in vitro, probably due to the limited ex vivo expansion capability of HSCs and hematopoietic multipotent progenitor cells (HMPCs). Human embryonic stem cells (hESCs) are pluripotent cells that can proliferate almost infi nitely in vitro (Thomson et al. 1998), and thus represent a potential source of platelets for transfusion and for studying the ontogeny of hematopoiesis (Ma et al. 2008; Takayama et al. 2008; Vodyanik et al. 2005; Wang et al. 2004; Yokoyama et al. 2009). It is well known, however, that repeated transfusion induces the production of antibodies against allogenic human leukocyte antigen (HLA) on the transfused platelets (Schiffer 2001), which renders the
Clinical Application Department, Center for iPS Cell Research and Application, Kyoto University, 606-8507, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. aEmail: naoya.takayama@cira.kyoto-u.ac.jp bEmail: kojieto@cira.kyoto-u.ac.jp *Corresponding author
patient unresponsive to platelet transfusion therapy. To avoid such immune reactions following multiple allogeneic platelet transfusions, it is desirable to use HLA-matched or autologous platelets. In this context, we propose that the use of HLA-matched human induced pluripotent stem cells (hiPSCs) may be an effective strategy for generating functional platelets for patients requiring repeated transfusion (Fig. 1). Furthermore, derivation of iPS cells from patients with congenital platelet abnormalities should contribute to a better understanding of the pathogenesis of these abnormalities, as well as to the development of gene correction therapies.
