A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells.
BACKGROUND
The efficient generation of hematopoietic stem cells (HSCs) from human-induced pluripotent stem cells (iPSCs) holds great promise in personalized transplantation therapies. However, the derivation of functional and transplantable HSCs from iPSCs has had very limited success thus far.


METHODS
We developed a synthetic 3D hematopoietic niche system comprising nanofibers seeded with bone marrow (BM)-derived stromal cells and growth factors to induce functional hematopoietic cells from human iPSCs in vitro.


RESULTS
Approximately 70 % of human CD34+hematopoietic cells accompanied with CD43+progenitor cells could be derived from this 3D induction system. Colony-forming-unit (CFU) assay showed that iPSC-derived CD34+cells formed all types of hematopoietic colonies including CFU-GEMM. TAL-1 and MIXL1, critical transcription factors associated with hematopoietic development, were expressed during the differentiation process. Furthermore, iPSC-derived hematopoietic cells gave rise to both lymphoid and myeloid lineages in the recipient NOD/SCID mice after transplantation.


CONCLUSIONS
Our study underscores the importance of a synthetic 3D niche system for the derivation of transplantable hematopoietic cells from human iPSCs in vitro thereby establishing a foundation towards utilization of human iPSC-derived HSCs for transplantation therapies in the clinic.
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Yulin
Y
Xu
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Wei
W
Shan
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Xia
X
Li
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Binsheng
B
Wang
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Senquan
S
Liu
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Yebo
Y
Wang
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Yan
Y
Long
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Ruxiu
R
Tie
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Limengmeng
L
Wang
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Shuyang
S
Cai
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Hao
H
Zhang
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Yu
Y
Lin
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Mingming
M
Zhang
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Weiyan
W
Zheng
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Yi
Y
Luo
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Xiaohong
X
Yu
Department of Diabetes and Metabolic Diseases Research, City of Hope, Duarte, CA, 91010, USA.
Jiing-Kuan
JK
Yee
Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Junfeng
J
Ji
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China. huanghe@zju.edu.cn.
He
H
Huang
Hematopoietic stem cells; Induced pluripotent stem cells; Niche; Three dimension; Transplantation
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