title: An effective and simple expansion system for megakaryocyte progenitor cells using a combination of heparin with thrombopoietin and interleukin-11.
abstract: Transfusion of ex vivo expanded megakaryocyte (MK) progenitor cells has been suggested to shorten the time of platelet recovery in the thrombocytopenia induced by radiotherapy or chemotherapy. Here, we report an effective and simple expansion system of MK progenitor cells from cord blood (CB) CD34(+) cells using a combination of thrombopoietin (TPO), interleukin (IL)-11, and heparin. When the CB CD34(+) cells were cultured in a liquid expansion system in the presence of TPO + recombination human (rh)IL-11 + heparin for 7 days, the number of CB CD34(+)/CD41a(+) cells was significantly increased compared to control groups (p < 0.05). When the suspension cells collected from 7-day liquid culture were replated in semisolid cultures, increased large MK colonies were observed in the culture with combination of TPO + IL-11 + heparin compared to those of control groups. In vivo, transfusion of CD34(+) cells expanded with TPO + IL-11 + heparin into irradiated nonobese diabetic/severe combined immunodeficient mice significantly accelerated platelet recovery. These data indicate that heparin as effective cofactor for TPO and IL-11 promotes expansion of MK progenitor cells from CB CD34(+) cells. This expansion system is simple and effective and could be used for the treatment of thrombocytopenia after radiotherapy or chemotherapy.
authors.affiliation: State Key Laboratory of Experimental Hematology, National Research Center of Stem Cell Engineering & Technology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People's Republic of China. tihzchan@public.tpt.tj.cn
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhi Jian
authors.initials: ZJ
authors.lastname: Xiao
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Cun Gang
authors.initials: CG
authors.lastname: Fan
authors.forename: Xiang Fei
authors.initials: XF
authors.lastname: Yuan
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D017690:Cell Transplantation; D015672:Erythroid Precursor Cells / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010976:Platelet Count; D013921:Thrombocytopenia / Q000628:therapy; D013926:Thrombopoietin / Q000494:pharmacology*; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D017370:Interleukin-11; D006493:Heparin; D013926:Thrombopoietin