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. Author manuscript; available in PMC: 2020 May 1.
Published in final edited form as: Blood Rev. 2019 Jan 28;35:7–17. doi: 10.1016/j.blre.2019.01.003

Table 2: Immunological barriers to pRBC xenotransfusion.

Barrier References Attempts to
overcome barrier		 References
Xenoantigenic barriers:Gal, Neu5Gc, Sda Gal:
Galili 1988 [53]
Cooper 1992 [54]
Good 1992 [55]
Doucet 2004 [56]

Neu5Gc:
Asaoka 1994 [57]
Bouhours 1996 [58]
Zhu 2002 [59]
Padler-Karavani 2011 [60]

Sda:
Byrne 2014 [61]
Byrne 2018 [62]
Zhao 2018 [63]		 Development of triple-knock out (TKO) pigs Phelps 2003 [49]
Kolber-Simonds 2004 [50]
Long 2009 [52]
Estrada 2015 [64]
Butler 2016 [65]
Lee 2016 [66]
Gao 2017 [31]
Wang 2017 [67]
Complement-mediated lysis CD55
Atkinson 1991 [68]
Dalmasso 1991 [69]
White 1995 [70]
Morgan 2005 [71]

CD46
Lublin 1988 [72]
Perez de la Lastra 1991 [73]
Thorley 1997 [74]

CD59
Sugita 1988 [75]
Rollins 1991 [76]		 Transgenic expression of human complement regulatory proteins, CD46 and CD55 Cozzi 1994 [77]
Fodor 1994 [78]
Langford 1994 [79]
McCurry 1995 [80]
Diamond 1996 [81]
Diamond 2001 [82]
Schuurman 2002 [83]
Loveland 2004 [84]
Hara 2008 [85]
Long 2009 [52]
van der Windt 2009 [86]
McGregor 2012 [87]
Burdorf 2014 [88]
Butler 2016 [65]
Lee 2016 [66]
Macrophage phagocytosis Qian 1999 [89]
Leonard 2000 [90]
Ide 2005 [91]
Long 2009 [52]		 Transgenic expression of human CD47 Ide 2007 [92]
Yang 2010 [93]
Navarro-Alvarez 2011 [94]
Maeda 2013 [95]
Tena 2014 [96]
Tena 2017 [97]
Natural killer (NK) cells Inverardi 1997 [98]
Baumann 2004 [99]
Kennett 2010 [100]		 Transgenic expression of HLA-G and/or HLA-E and/or Cw3 Dorling 2000 [101]
Matsunami 2001 [102]
Forte 2005 [103]
Crew 2007 [104]
Weiss 2009 [105]
Maeda 2013 [95]
Esquivel 2015 [107]
T-cell-mediated immune
response 		Gill 1994 [107]
Rollins 1994 [108]
Elwood 1998 [109]
Yamada 2005 [110]
Davila 2006 [111]
Koshika 2011 [112]
Ezzelarab 2014 [113]
Griesemer 2014 [114]
Ezzelarab 2015 [115]		 CD154 and CD40 blockade-based immunosuppressive therapy











Transgenic expression of CTLA4-Ig



CIITA-knockdown


SLA class 1-KO		 Buhler 2000 [116]
Kuwaki 2004 [117]
Tseng 2005 [118]
Ezzelarab 2012 [119]
Mohiuddin 2014 [120]
Iwase 2015 [121, 122]
Mohiuddin 2016 [123]
Bottino 2017 [124]
Iwase 2017 [125]
Kim 2017 [126]
Shin 2018 [127]

Martin 2005 [128]
Phelps 2009 [129]
Bottino 2014 [130]

Hara 2013 [131]
Iwase 2015 [132]

Reyes 2014 [133]