Notes[N1] Michelle Valentina Smith née Michael Valentine Smith.

[N2] Ovaries and uterus.

[N3] Michelle V. Smith on Oprah.

[N4] CBS Nightly News.

[N5] Oprah Winfrey, Ellen, Two and a Half Men, CSI, Survivor, Late Late Show with Craig Ferguson, et al.

[N6] Smith, interview in L’Osservatore Romano.

FundingThe initial research was supported by grants from the National Institutes of Health and the National Institute of Biomedical Imaging and Bioengineering.

Contributors Hopkins collaborators on the research include postdoctoral scholars Thomas Paul Jefferson, MD, Edward McChang, MD, Hugh Bonillas, MD, and L. J. Thompson, PhD Neurobiological Engineering, John Varley University, Farside Station, RM.

Citation Engineering of reproductive tissues using autologous microcirculatory beds as vascularized bioscaffolds for organ construction. Thomas P. Jefferson, Edward McChang, Robert G. Bonillas, L. J. Thompson. TANSTAAFL 2048; 23(3): 01042009. doi: 10.1096/apr.01.fo.ols.08-114868 .

Abstract

Classic tissue engineering paradigms are limited by the incorporation of a functional vasculature and a reliable means for reimplantation into the host circulation. We have developed a novel approach to overcome these obstacles using autologous explanted microcirculatory beds (EMBs) as bioscaffolds for engineering complex three-dimensional constructs. Based on this approach, we have successfully cloned ovaries and uterus from the stem cells of a forty year old post-operative woman born transsexual who wished to become pregnant. EMBs consisting of an afferent artery, capillary beds, efferent vein, and surrounding parenchymal tissue are explanted and maintained for 24 h ex vivo in a bioreactor that preserves EMB viability and function. Given the rapidly advancing field of stem cell biology, EMBs were subsequently seeded with three distinct stem cell populations, multipotent adult progenitor cells (MAPCs), and bone marrow and adipose tissue-derived mesenchymal stem cells (MSCs). We demonstrate MAPCs, as well as MSCs, are able to egress from the microcirculation into the parenchymal space, forming proliferative clusters. Likewise, human adipose tissue-derived MSCs were also found to egress from the vasculature and seed into the EMBs, allowing viable natural fertilization of the subsequent ova. We further demonstrate that MSCs can be transfected to express a luciferase protein and continue to remain viable and maintain luciferase expression in vivo. By using the vascular network of EMBs, EMBs can be perfused ex vivo and seeded with stem cells, differentiating direction into neo-organs or transfected to replace failing organs and deficient proteins.