High dose chemotherapy and transplantation of hematopoietic progenitors from murine D3 embryonic stem cells.
Differentiating embryonic stem (ES) cells are an increasingly important source of hematopoietic progenitors, useful for both basic research and clinical applications. To date, characteristics of specific factors capable of influencing hematopoietic cell fate from ES cells remains elusive. We report that mMSC Feeder Layer and the combination of VEGF, SCF and TPO strongly promote hematopoietic differentiation. The results showed that the cells induced from ES-D3 expressed hematopoietic progenitor antigens (CD34 and CD117), myelocyte cell antigen (CD11b), erythrocyte cell antigen (Ter119), and transcription factors (Flk-1, GATA-2, SCL, beta-H1 and beta-major). Furthermore, those induced differentiated cells were injected into female C57BL/6 mice which were treated with high dose topotecan chemotherapy to restore part of their blood system function. We observed rapid white blood cell recovery, which suggested that the infusion of differentiated cells has a positive impact on hematopoiesis. The Sry gene in peripheral blood, bone marrow and spleen of transplanted female mice was confirmed by PCR analysis, which affirmed the existence of the chimera.
Jiang
Jingyan
J
Qilu Hospital, Shandong University, Jinan, China.
Kong
Beihua
B
Shen
Baijun
B
Li
Li
L
Yang
Xingsheng
X
Hou
Huaishui
H
Shi
Qing
Q
Ma
Daoxin
D
Ma
Xiufeng
X
D000818:Animals; D000954:Antigens, Surface; D000970:Antineoplastic Agents / Q000009:adverse effects; D001755:Blastocyst / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019089:Stem Cell Factor / Q000502:physiology*; D033581:Stem Cell Transplantation; D013926:Thrombopoietin / Q000502:physiology*; D019772:Topotecan / Q000009:adverse effects; D014157:Transcription Factors / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
D000954:Antigens, Surface; D000970:Antineoplastic Agents; D019089:Stem Cell Factor; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D019772:Topotecan; D013926:Thrombopoietin