Implantable microenvironments to attract hematopoietic stem/cancer cells

被引:87
作者
Lee, Jungwoo [1 ,2 ,3 ]
Li, Matthew [1 ,2 ,3 ,4 ]
Milwid, Jack [1 ,2 ,3 ,4 ]
Dunham, Joshua [5 ]
Vinegoni, Claudio [5 ]
Gorbatov, Rostic [5 ]
Iwamoto, Yoshiko [5 ]
Wang, Fangjing [1 ,2 ,3 ]
Shen, Keyue [1 ,2 ,3 ]
Hatfield, Kimberley [6 ]
Enger, Marianne [7 ]
Shafiee, Sahba [8 ]
McCormack, Emmet [8 ]
Ebert, Benjamin L. [9 ,10 ]
Weissleder, Ralph [5 ]
Yarmush, Martin L. [1 ,2 ,11 ]
Parekkadan, Biju [1 ,2 ,3 ,10 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA
[3] Shriners Hosp Children, Boston, MA 02114 USA
[4] Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA
[5] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA
[6] Haukeland Hosp, Dept Med, Sect Hematol, N-5021 Bergen, Norway
[7] Univ Bergen, Gade Inst, N-5020 Bergen, Norway
[8] Univ Bergen, Haukeland Univ Hosp, Inst Internal Med, Dept Hematol, N-5020 Bergen, Norway
[9] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Hematol, Boston, MA 02114 USA
[10] Harvard Stem Cell Inst, Boston, MA 02115 USA
[11] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA
基金
美国国家卫生研究院;
关键词
hydrogel scaffolds; leukemia; mesenchymal stem cells; stem cell niche; tissue engineered bone marrow; INVERTED COLLOIDAL CRYSTALS; MESENCHYMAL STEM-CELLS; BONE-MARROW; EXTRAMEDULLARY HEMATOPOIESIS; STEM/PROGENITOR CELLS; PROGENITOR CELLS; NICHE; TISSUES; REGENERATION; ENGRAFTMENT;
D O I
10.1073/pnas.1208384109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
The environments that harbor hematopoietic stem and progenitor cells are critical to explore for a better understanding of hematopoiesis during health and disease. These compartments often are inaccessible for controlled and rapid experimentation, thus limiting studies to the evaluation of conventional cell culture and transgenic animal models. Here we describe the manufacture and image-guided monitoring of an engineered microenvironment with user-defined properties that recruits hematopoietic progenitors into the implant. Using intravital imaging and fluorescence molecular tomography, we show in real time that the cell homing and retention process is efficient and durable for short-and long-term engraftment studies. Our results indicate that bone marrow stromal cells, precoated on the implant, accelerate the formation of new sinusoidal blood vessels with vascular integrity at the micro-capillary level that enhances the recruitment hematopoietic progenitor cells to the site. This implantable construct can serve as a tool enabling the study of hematopoiesis.
引用
收藏
页码:19638 / 19643
页数:6
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