ARE PROFESSIONAL ANTIGEN PRESENTING CELLS (APCs) NECESSARY TO INITIATE GRAFT REJECTION?

Dharnidharka, Vikas R.; Briscoe, David M.; Isaacs, Cary; Downing, Greg; Prosky, Stefan; Parenteau, Nancy L.; Hardin-Young, Janet

doi:10.1097/00007890-199806270-00667

Cited by 1 publication

(1 citation statement)

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“…60 In contrast, Apligraf, an avascular bilayered skin equivalent approved by FDA, does not induce acute rejection responses likely due to the fact that it lacks both professional antigenpresenting cells and ECs. [61][62][63] While grafts containing unmodified human ECs will be alloimmunogenic, this property can be eliminated from HECFC-derived ECs by CRISPR/Cas9mediated deletion of HLA antigen expression. [64][65][66] We anticipate that successful engraftment of a 3D bioprinted human skin graft by incorporating allogeneic ECs without triggering rejection in the host would be of great clinical utility and the basis for the creation of an ''off-the-shelf'' clinical product.…”

Section: D Bioprinting Of Vascularized Human Skin Graftmentioning

confidence: 99%

Three Dimensional Bioprinting of a Vascularized and Perfusable Skin Graft Using Human Keratinocytes, Fibroblasts, Pericytes, and Endothelial Cells

Baltazar

Merola

Catarino

et al. 2020

Tissue Engineering Part A

191

197

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Multilayered skin substitutes comprising allogeneic cells have been tested for the treatment of nonhealing cutaneous ulcers. However, such nonnative skin grafts fail to permanently engraft because they lack dermal vascular networks important for integration with the host tissue. In this study, we describe the fabrication of an implantable multilayered vascularized bioengineered skin graft using 3D bioprinting. The graft is formed using one bioink containing human foreskin dermal fibroblasts (FBs), human endothelial cells (ECs) derived from cord blood human endothelial colony-forming cells (HECFCs), and human placental pericytes (PCs) suspended in rat tail type I collagen to form a dermis followed by printing with a second bioink containing human foreskin keratinocytes (KCs) to form an epidermis. In vitro, KCs replicate and mature to form a multilayered barrier, while the ECs and PCs self-assemble into interconnected microvascular networks. The PCs in the dermal bioink associate with EC-lined vascular structures and appear to improve KC maturation. When these 3D printed grafts are implanted on the dorsum of immunodeficient mice, the human EC-lined structures inosculate with mouse microvessels arising from the wound bed and become perfused within 4 weeks after implantation. The presence of PCs in the printed dermis enhances the invasion of the graft by host microvessels and the formation of an epidermal rete.

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