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Massachusetts General Hospital, Harvard Medical School, Shriners Hospital for Children

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Proc. Natl. Acad. Sci. USA, November 27, 2012 vol. 109 no. 48 19638-19643. Published online before print November 12, 2012, doi: 10.1073/pnas.1208384109 Implantable microenvironments to attract hematopoietic stem/cancer cells

Abstract

Jungwoo Lee^a, Matthew Li^a,b, Jack Milwid^a,b, Joshua Dunham^c, Claudio Vinegoni^c, Rostic Gorbatov^c, Yoshiko Iwamoto^c, Fangjing Wang^a, Keyue Shen^a, Kimberley Hatfield^d, Marianne Enger^e, Sahba Shafiee^f, Emmet McCormack^f, Benjamin L. Ebert^g,h, Ralph Weissleder^c, Martin L. Yarmush^a,i, and Biju Parekkadan^a,h,1

^aCenter for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children in Boston, MA 02114;
^bHarvard-MIT Health Sciences and Technology, Cambridge, MA 02139;
^cCenter for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;
^dSection of Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway;
^eGade Institute, University of Bergen, 5020 Bergen, Norway;
^fDepartment of Hematology, Institute of Internal Medicine, Haukeland University Hospital, University of Bergen, 5020 Bergen, Norway;
^gDepartment of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02114;
^hThe Harvard Stem Cell Institute, Boston, MA 02115; and
ⁱDepartment of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854

Edited by Mina J. Bissell, E. O. Lawrence Berkeley National Laboratory, Berkeley, CA, and approved October 22, 2012 (received for review May 21, 2012)

Abstract
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 microcapillary level that enhances the recruitment hematopoietic progenitor cells to the site. This implantable construct can serve as a tool enabling the study of hematopoiesis.

hydrogel scaffolds, leukemia, mesenchymal stem cells, stem cell niche, tissue engineered bone marrow

Footnotes
¹To whom correspondence should be addressed.

Author contributions: J.L., B.L.E., R.W., M.L.Y., and B.P. designed research; J.L., M.L., J.M., J.D., C.V., R.G., Y.I., F.W., K.S., K.H., M.E., S.S., E.M., and B.P. performed research; E.M., B.L.E., and R.W. contributed new reagents/analytic tools; J.L., E.M., and B.P. analyzed data; and J.L. and B.P. wrote the paper.

논문정보

형식Research article
게재일2012년 11월 (BRIC 등록일 )
연구진국외 연구진
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