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In the context of HEAVEN,[5] the donor body would reject the head (although it cannot be excluded that resident head immune cells in the head can mount a reaction against the body), with rejection of tissues not protected by the blood–brain barrier (i.e., the brain) such as the pituitary gland or the spinal cord (and of course the face skin and muscles) especially critical. This necessitates IS with a protocol similar to facial and limb transplants. Sirolimus, with its minimal neurotoxicity and pro-neuroregenerative properties (despite its interference with wound healing), is especially indicated. However, long-term administration of these medications results – as is well known – in significant morbidity and mortality, including nephrotoxicity, infections, neoplasm, and cardiovascular diseases. Equally important, chronic rejection (graft-versus-host-disease [GVHD]) is not prevented, even with maximal IS. Therefore, induction of allograft tolerance – so that no drug is required – is a sine-qua-non, as previously indicated.[4] In the 21st century, tolerance induction through chimerism (full or partial) is a clinical reality. Tolerance to HLA matched and mismatched living donor kidney transplants with complete withdrawal of IS drugs without subsequent rejection for up to 14 years of observation has been achieved in more than 50 patients enrolled in trials in four medical centers after the establishment of transient or persistent chimerism (with nonmyeloablative conditioning regimens employing thymoglobulin, belatacept, and bone marrow transplantation plus rituximab). Complete drug withdrawal without chimerism was reported in a prospective trial of liver transplantation combined with injection of regulatory T cells. IS drug minimization without rejection was reported in recipients of living donor kidney transplants after injection of recipient regulatory T cells or injection of donor regulatory monocytes or dendritic cells.[10] In one HEAVEN scenario,[14] the donor’s bone marrow would be populated with the bone marrow cells of the recipient after the donor is sublethally irradiated (with vital organs shielding), including the thymus, and its periphery is depleted of donor T cells (with Thymoglobulin), B cells (with Rituximab), plasma cells (with Carfilzomib), and macrophages (with Alemtuzumab). Thereafter, the body is immunologically reconstituted with the recipient’s bone marrow and www.surgicalneurologyint.com

Advancing the technology for head transplants: From immunology to peripheral nerve fusion