In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism

Yu Ru Shih, Heemin Kang, Vikram Rao, Yu Jui Chiu, Seong Keun Kwon, Shyni Varghese

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engineer bone tissues with a functional bone marrow (BM) compartment in vivo by using a synthetic biomaterial with spatially differing cues. Specifically, we have developed a synthetic matrix recapitulating the dual-compartment structures by modular assembly of mineralized and nonmineralized macroporous structures. Our results show that these matrices incorporated with BM cells or BM flush transplanted into recipient mice matured into functional bone displaying the cardinal features of both skeletal and hematopoietic compartments similar to native bone tissue. The hematopoietic function of bone tissues was demonstrated by its support for a higher percentage of mixed chimerism compared with i.v. injection and donor hematopoietic cell mobilization in the circulation of nonirradiated recipients. Furthermore, hematopoietic cells sorted from the engineered bone tissues reconstituted the hematopoietic system when transplanted into lethally irradiated secondary recipients. Such engineered bone tissues could potentially be used as ectopic BM surrogates for treatment of nonmalignant BM diseases and as a tool to study hematopoiesis, donor-host cell dynamics tumor tropism, and hematopoietic cell transplantation.

Original languageEnglish
Pages (from-to)5419-5424
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number21
DOIs
Publication statusPublished - 2017 May 23
Externally publishedYes

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Keywords

  • Bone marrow
  • Mixed chimerism
  • Regenerative medicine
  • Stem cells
  • Tissue engineering

ASJC Scopus subject areas

  • General

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