Table 1 Summary of study characteristics of included studies
From: Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review
| Â | Â | Animal model characteristics | Cell characteristics | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
Reference | Country | Species (strain) | Intervention (days) | Follow-up (days) | Stem cell type | Cell species of origin | Tissue of origin for cell product | Transplant type | Dose | Route | Cell enhancement |
Nagaya 2003 [32] | Japan | Rat (nude athymic) | 7 | 14 | EPC | Human | Umbilical cord blood | Xenogenic | 1,000,000 | IV (intrajugular) | Adrenomedullin transfection |
Takahashi 2004 [19] | Japan | Dog (beagle) | 14 | 28 | EPC | Dog | Peripheral blood | Autologous | 1,000,000 | IV (intrajugular) | Â |
Zhao 2005a [33] | Canada | Rat (Fischer) | 21 | 14 | EPC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (intrajugular) | eNOS |
Zhao 2005b [33] | Canada | Rat (Fischer) | 3 | 21 | EPC | Rat | Bone marrow | Allogeneic | 1,500,000 | IV (intrajugular) | Â |
Kanki-Horimoto 2006 [34] | Japan | Rat (Sprague Dawley) | 7 | 14 | MSC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (intrajugular) | Â |
Baber 2007 [35] | USA | Rat (Sprague Dawley) | 14 | 35 | MSC | Rat | Bone marrow | Allogeneic | 3,000,000 | Intratracheal | Â |
Spees 2008 | USA | Rat (Sprague Dawley) | 21 | 21 | BM-MNC | Rat | Bone marrow | Allogeneic | 5,000,000 | IV (tail vein) | Â |
Yip 2008a [36] | Taiwan | Rat (Sprague Dawley) | 7 | 83 | EPC | Rat | Bone marrow | Autologous | 1,200,000 | IV (tail vein) | Â |
Yip 2008b [36] | Taiwan | Rat (Sprague Dawley) | 7 | 21 | EPC | Rat | Bone marrow | Autologous | 1,200,000 | IV (tail vein) | Â |
Sun 2009a [37] | Taiwan | Rat (Sprague Dawley) | 3 | 42 | EPC | Rat | Bone marrow | Autologous | 2,000,000 | IV (tail vein) | Cilostazol pretreatment |
Sun 2009b [37] | Taiwan | Rat (Sprague Dawley) | 3 | 42 | EPC | Rat | Bone marrow | Autologous | 2,000,000 | IV (tail vein) | Â |
Umar 2009 [38] | Netherlands | Rat (Wistar) | 14 | 14 | MSC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (intrajugular) | Â |
Ormiston 2010 [22] | Canada | Rat (nude athymic) | 3 | 21 | EPC (early and late) | Human | Peripheral blood | Xenogenic | 1,500,000 | IV (intrajugular) | Â |
Takemiya 2010 [39] | Japan | Rat (Lewis) | 14 | 28 | MSC | Rat | Bone marrow | Allogeneic | 500,000 | IV (tail vein) | PCS transfection |
Angelini 2011 [40] | Italy | Rat (Sprague Dawley) | 28 | 7 | MSC | Rat | Adipose | Allogeneic | 4,000,000 | IV (tail vein) | Â |
Mirsky 2011a [41] | USA | Rat (nude athymic) | 35 | 10 and 15 | EPC | Human | Peripheral blood | Xenogenic | 1,500,000 | IV (tail vein) | Â |
Mirsky 2011b [41] | USA | Rat (nude athymic) | 35 | 10 and 15 | EPC | Human | Peripheral blood | Xenogenic | 1,500,000 | IV (tail vein) | Â |
Jiang 2012 [42] | China | Rat (Sprague Dawley) | 3 | 18 | MSC | Â | Bone marrow | Allogeneic | 4,000,000 | IV (tail vein) | Â |
Kim 2012 [43] | Korea | Rat (Sprague Dawley) | 7 | 28 | BM-MNC | Rat | Bone marrow | Allogeneic | 20,000,000 | IV (tail vein) | Â |
Luan 2012 [30] | China | Rat (Sprague Dawley) | 21 | 14 | MSC | Rat | Bone marrow | Allogeneic | 100,000 | IV (right femoral vein) | Â |
Luan 2012 [20] | China | Dog (Mongrel) | 14 | 56 | BM-MNC | Dog | Bone marrow | Allogeneic | 1,300,000 | Intratracheal | Â |
Sun 2012 [44] | Taiwan | Rat (Sprague Dawley) | 3 | 35 | EPC | Rat | Bone marrow | Autologous | 2,000,000 | IV (tail vein) | Â |
Xie 2012 [45] | China | Rat (Sprague Dawley) | 7 | 14 | MSC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (right femoral vein) | Â |
Yen 2013 [46] | Taiwan | Rat (Sprague Dawley) | 21 | 69 | EPC | Rat | Bone marrow | Autologous | 2,000,000 | IV (penile vein) | Â |
Zhou 2013a [47] | USA | Rat (Fischer) | 3 | 25 | EPC | Rat | Bone marrow | Allogeneic | 1,500,000 | IV (intrajugular) | COX1-PCS transfection |
Zhou 2013b [47] | USA | Rat (Fischer) | 21 | 28 | EPC | Rat | Bone marrow | Allogeneic | 1,500,000 | IV (intrajugular) | COX1-PCS transfection |
Chen 2014 [48] | China | Rat (Sprague Dawley) | 21 | 14 | MSC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (tail vein) | Â |
Eguchi 2014 [49] | Japan | Rat (Wistar) | 7 | 21 | MSC | Rat | Adipose | Allogeneic | 7,000,000 | IV (tail vein) | Â |
Guo 2014 [50] | China | Rat (Sprague Dawley) | 21 | 21 | MSC | Rat | Bone marrow | Allogeneic | 5,000,000 | IV (intrajugular) | Â |
Luan 2014 [51] | China | Rat (Sprague Dawley) | 7 | 173 | MSC | Rat | Bone marrow | Allogeneic | 10,000,000 | IV (sublingual vein) | Â |
Somanna 2014 [52] | USA | Rat (Sprague Dawley) | 14 | 14 | MSC | Rat | Adipose | Allogeneic | 3,000,000 | Intratracheal | COX1 transfection |
Ikutomi 2015a [53] | Japan | Rat (Fischer) | 0, 1, 3, 5, 7, 9 | 19 | EPC-early | Rat | Bone marrow | Allogeneic | 1 × 106 per injection (total 6×) | IV (tail vein) |  |
Ikutomi 2015b [53] | Japan | Rat (Fischer) | 0, 1, 3, 5, 7, 9 | 19 | EPC-late | Rat | Bone marrow | Allogeneic | 1 × 106 per injection (total 6×) | IV (tail vein) |  |
Ikutomi 2015c [53] | Japan | Rat (Fischer) | 0, 1, 3, 5, 7, 9 | 19 | EPC-very late | Rat | Bone marrow | Allogeneic | 1 × 106 per injection (total 6×) | IV (tail vein) |  |
Kang 2015 [54] | Korea | Rat (Lewis) | 14 | 14 | MSC | Human | Umbilical cord blood | Allogeneic | 250,000 | IV (tail vein) | S1p priming |
Lee 2015 [55] | Korea | Rat (Sprague Dawley) | 7 | 7 | MSC | Human | Umbilical cord blood | Xenogenic | 3,000,000 | IV (intrajugular) | Â |
Liang 2015 [56] | China | Rat (Sprague Dawley) | 7 or 14 | 7 | MSC | Rat | Adipose | Allogeneic | 1,000,000 | IV (intrajugular) | Â |
Liu 2015 [57] | China | Rat (Sprague Dawley) | 5 | 16 | MSC | Human | Umbilical cord blood | Xenogenic | 1,000,000 | IV (tail vein) | Â |
Luo 2015 [58] | China | Rat (Sprague Dawley) | 14 | 7 | MSC | Rat | Adipose | Allogeneic | 1,000,000 | IV (intrajugular) | Â |
Pan 2015 [59] | China | Rat (Sprague Dawley) | 7, 14, 21 | 7,14,21 | EPC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (tail vein) | shRNA-CD40 transfection |
Chen 2016a [60] | China | Rat (Wistar) | 14 | 21 | MSC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (tail vein) | eNOS/F92A-Cav1 |
Chen 2016b [60] | China | Rat (Wistar) | 14 | 21 | MSC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (tail vein) | F92A-Cav1 |
Chen 2016c [60] | China | Rat (Wistar) | 14 | 21 | MSC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (tail vein) | eNOS |
Huang 2016 [61] | Taiwan | Rat (Sprague Dawley) | 0 or 14 | 14 | iPSC | Mouse | Not reported | Xenogenic | 2,000,000 | IV (tail vein) | None (compared to conditioned media) |
Kim 2016 [62] | Korea | Rat (Sprague Dawley) | 7 | 7 and 21 | MSC | Human | Umbilical cord blood | Xenogenic | 3 × 106/ml/cm2 | IV (intrajugular) |  |
Lim 2016 [63] | Korea | Rat (Lewis) | 14 | 14 | MSC | Human | Bone marrow | Xenogenic | 250,000 | IV (tail vein) | C1P (ceramide-1 phosphate) priming |
Rathinasabapathy 2016 [64] | USA | Rat (Sprague Dawley) | 14 | 14 | MSC | Rat | Adipose | Allogeneic | 1,000,000 | IP | Â |
Varshney 2016 [65] | USA | Rat (Sprague Dawley) | 3 | 18 | MSC | mouse | Not reported | Xenogenic | 3,500,000 | IV (intrajugular) | GFP-SKL (secreted Klotho) transfection |
Ahmed 2017 [66] | Egypt | Rat (Wistar) | 14 | 14 | EPC | Rat | Bone marrow | Allogeneic | 1,000,000 | IV (no specific site indicated) | pinocembrin preconditioning |
Cheng 2017 [67] | China | Rat (Lewis) | 21 | 21 | MSC | Rat | Bone marrow | Allogeneic | 3,000,000 | IV (tail vein) | Let7a transfection |
de Mendonca 2017 [68] | Brazil | Rat (Wistar) | 14 | 21 | MSC | Rat | Adipose | Allogeneic | 100,000 | IV (intrajugular) | Â |
Lee 2017 [69] | Korea | Rat (Sprague Dawley) | 1, 7 | 14 and 28 | MSC | Human | Umbilical cord blood | Xenogenic | 3,000,000, 1,000,000, 300,000 | IV (intrajugular) (multiple doses and timing) | Â |
Middleton 2017 [70] | USA | Rat (Sprague Dawley) | 14 | 21 | CDC | Rat | Heart | Allogeneic | 2,000,000 | IV (intrajugular) | Â |
Luo 2018 [71] | China | Rat (Sprague Dawley) | 14 | 21 | MSC | Rat | Adipose | Allogeneic | 1,000,000 | IV (intrajugular) | Adiponectin transfection |