@article{SchattonYangKleffeletal.2015,
  author    = {Schatton, Tobias and Yang, Jun and Kleffel, Sonja and Uehara, Mayuko and Barthel, Steven R. and Schlapbach, Christoph and Zhan, Qian and Dudeney, Stephen and Mueller, Hansgeorg and Lee, Nayoung and de Vries, Juliane C. and Meier, Barbara and Beken, Seppe Vander and Kluth, Mark A. and Ganss, Christoph and Sharpe, Arlene H. and Waaga-Gasser, Ana Maria and Sayegh, Mohamed H. and Abdi, Reza and Scharffetter-Kochanek, Karin and Murphy, George F. and Kupper, Thomas S. and Frank, Natasha Y. and Frank, Markus H.},
  title     = {ABCB5 Identifies Immunoregulatory Dermal Cells},
  series = {Cell Reports},
  volume    = {12},
  journal   = {Cell Reports},
  doi       = {10.1016/j.celrep.2015.08.010},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149989},
  pages     = {1564 -- 1574},
  year      = {2015},
  abstract  = {Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5\(^+\) DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5\(^+\) DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.},
  language  = {en}
}
@article{TappenbeckSchroederNiebergallRothetal.2019,
  author    = {Tappenbeck, Nils and Schr{\"o}der, Hannes M. and Niebergall-Roth, Elke and Hassinger, Fathema and Dehio, Ulf and Dieter, Kathrin and Kraft, Korinna and Kerstan, Andreas and Esterlechner, Jasmina and Frank, Natasha Y. and Scharffetter-Kochanek, Karin and Murphy, George F. and Orgill, Dennis P. and Beck, Joachim and Frank, Markus H. and Ganss, Christoph and Kluth, Mark A.},
  title     = {In vivo safety profile and biodistribution of GMP-manufactured human skin-derived ABCB5-positive mesenchymal stromal cells for use in clinical trials},
  series = {Cytotherapy},
  volume    = {21},
  journal   = {Cytotherapy},
  doi       = {10.1016/j.jcyt.2018.12.005},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240456},
  pages     = {546-560},
  year      = {2019},
  abstract  = {Background aims Human dermal ABCB5-expressing mesenchymal stromal cells (ABCB5+ MSCs) represent a promising candidate for stem cell-based therapy of various currently uncurable diseases in several fields of regenerative medicine. We have developed and validated a method to isolate, from human skin samples, and expand ABCB5+ MSCs that meet the guideline criteria of the International Society for Cellular Therapy. We are able to process these cells into a Good Manufacturing Practice-conforming, MSC-based advanced-therapy medicinal product. Methods To support the development of ABCB5+ MSCs for potential therapeutic topical, intramuscular and intravenous administration, we have tested our product in a series of Good Laboratory Practice-compliant nonclinical in-vivo studies addressing all relevant aspects of biosafety, including potential long-term persistence and proliferation, distribution to nontarget tissues, differentiation into undesired cell types, ectopic tissue formation, tumor formation and local tissue reaction. Results (i) Subcutaneous application of 1 × 107 ABCB5+ MSCs/animal and intravenous application of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice did not result in safety-relevant biodistribution, persistence or proliferation of the cells; (ii) three monthly subcutaneous injections of ABCB5+ MSCs at doses ranging from 1 × 105 to 1 × 107 cells/animal and three biweekly intravenous injections of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice were nontoxic and revealed no tumorigenic potential; and (iii) intramuscular injection of 5 × 106 ABCB5+ MSCs/animal to immunocompromised mice was locally well tolerated. Discussion The present preclinical in vivo data demonstrate the local and systemic safety and tolerability of a novel advanced-therapy medicinal product based on human skin-derived ABCB5+ MSCs.},
  language  = {en}
}