Table 4.
Summary of in vivo performance of recellularized-decellularized vascular grafts since 2001.
| Author | Tissue Source | Cell Type | Bioreactor | Cell Number or Density | Animal Model | Patency Rate (%) | Histology (Endothelialization/Remodeling) |
|---|---|---|---|---|---|---|---|
| Decellularized allogenic vascular graft with autologous EC or EPC recellularization | |||||||
| Teebken (2001) [144] | Porcine carotid artery | Autologous EC | ? | ? | Porcine carotid artery | 54% and 71% at 1 and 4 months | Superior patency to polydioxanone prostheses but inferior to the arterial autograft. |
| Leyh (2006) [140] | Ovine pulmonary artery | Autologous EC | 12 h, 0.1 rpm; total 3 cycles |
1 × 106 | Ovine pulmonary artery (iv. heparin 400 IU/kg) | 100% at 6 months (seeded and non-seeded) | Cell infiltration and extracellular matrix similar to native artery in cell seeding group; Degeneration change was noted at control group |
| * Zhou (2012) [132] | Canine carotid artery | Autologous EPC | Yes | ? | Canine carotid artery | 95% at 3 months (control: 60%) | Smaller hyperplastic neointima area at mid-portion and anastomotic sites |
| Decellularized allogenic vascular graft with allogenic EC recellularization | |||||||
| Borschel (2005) [27] | Rat Iliac artery | Allogenic ECs | No | 106/100 μL | Rat femoral artery | 89% at 4 weeks (control 29%) | Complete ECs at lumen; SMCs repopulated vessel wall; Mechanical properties comparable to native vessel |
| Dall’Olmo (2014) [116] | Rat iliac artery | Allogenic ECs | No | 4 × 105/cm2 | Rat abdominal aorta | 100% at 3 months | ECs completely covered luminal surface at 1 month; Vascular wall remodeling at 3 months |
| Decellularized allogenic vascular graft with dual cell recellularization | |||||||
| Cho (2005) [131] | Canine carotid artery | Autologous bone marrow –derived cells differentiated EC, SMC | No | EC (1 × 107 cells/mL) SMC (3 × 107 cells/mL |
Canine carotid artery | 100% at 8 weeks (non-seeded occluded at 2 weeks) | Endothelium regeneration; Regeneration of three layer structure; Bone marrow derived cells were detected |
| # Cho (2006) [43] | Canine abdominal aorta | Autologous bone marrow-derived cells different to EC, SMC | ? | ? | Canine abdominal aorta | 100% (both G-CSF and non G-CSF groups) at 8 weeks | Endothelium formation was more extensive in the G-CSF-treated graft; Intimal hyperplasia was significantly reduced in the G-CSF-treated grafts |
| Narita (2008) [133] | Canine ureter | Canine EC & myofibroblast | ? | ? | Canine carotid artery | 100% at 6 months (control: 0%) | Non-seeded & PTFE grafts become occluded within a week |
| Yang (2009) [134] | Canine carotid artery | Autologous ECs and SMCs | Yes | ? | Canine carotid artery | 100% at 6 months | Similar macroscopic appearance to that of native vessels; High cell density and development of a highly organized structure of ECM. |
| Zhao (2010) [141] | Ovine carotid artery | Autologous MSC derived EC and SMC | No | SMC (2 × 107/mL); EC (1 × 107/mL) |
Sheep carotid artery | 100% at 2 & 5 months | The existence of endothelium, smooth muscle and the presence of collagen and elastin both at 2 and 5 months; The MSC derived cells survived and contributed to the vascular tissue regeneration |
| Dahan (2017) [31] | Porcine carotid artery | Allogenic EC and SMC | 50 mL/min and 80 mmHg | 0.5–1 × 105 cells/cm2 | Porcine carotid artery (iv. heparin 100 IU/kg) | 100% at 6 weeks (control: 100% but ~20% lumen stenosis) | No intimal hyperplasia, no thrombosis; Lack of neutrophils, macrophages, multinucleated giant cells, and B cells within these grafts; Well-organized host-recruited SMCs were observed in the media layer with a continuous monolayer of ECs on the lumen |
| Sagban (2011) [135] | Canine vein | EPCs from bone marrow and SMCs | ? | ? | Canine carotid artery | 90% at 3 months | A complete incorporation in the surrounding tissue; No aneurysm degeneration |
| Neff (2011) [145] | Porcine carotid artery | Autologous EC/SMC | 9.9 dyne/cm2~13.2 dyne/cm2 | EC (2 × 106/mL); SMC (5 × 105/mL) |
Porcine femoral or carotid artery (iv. heparin 100 IU/kg) | 100% at 4 months (both dual seeding and EC only) | More tissue maturation in dual-seeding group; More SMCs infiltration in dual-seeding group; Better contractile function in dual-seeding group |
| Wong (2015) [106] | Mouse aorta | Human iPS cell differentiated ECs & SMCs | 20–35 mL/min for 24 h | 5 × 105 | Mouse carotid artery | 60% at 3 weeks | Presence of human partially induced stem cell-derived; Endothelial/smooth muscle cells and host macrophage infiltration at 3 weeks |
| Decellularized xenogenic vascular graft with recellularization | |||||||
| Kaushal (2001) [9] | Porcine iliac artery | Autologous EPC | 1–25 dyne/cm2 | 1 × 105 cell/cm2 | Sheep carotid artery | 100% at 130 days (control: 25% at 15 days) | Confluent endothelialization; EPCs covered approximately 80% and 10% of the graft lumen, at 15 and 130 days; Functional SMCs at 130 days |
| Ma (2017) [56] | Fetal pig aorta | Allogenic ECs | 20–60 mL/min | 3 × 106/mL | Canine carotid artery | 100% at 6 months | No stenosis, expansion or thrombosis; Neointima (ECs) and neomedia (SMCs) reconstitution |
| Gene-modified cell recellularized vascular graft | |||||||
| Zhu (2008) [117] | Porcine carotid artery | Allogenic A20- regulated EPC differentiated EC and SMC | SMC (pulsatile radial stress 150 beats/min) EC (1–3 × 10−2 N/m2) | SMC (107/mL); EC (3 × 106/mL); |
Rat carotid artery | 100% at 6 months (control: 0%) | No inflammatory response; No stenosis or intimal thickening; Fewer apoptotic cells. |
| Mclhenny (2015) [125] | Human saphenous vein | Autologous ASC (transfected Ad-eNOS gene) | 1.5 dynes/cm2 at 0.2 Pa/day | 2 × 105 cells/cm2 | Rabbit abdominal aorta (iv. heparin 100 IU/kg) | 100% at 2 months (control: 100% but fibrin+) | An intact luminal cell layer without evidence of fibrin formation; Wall thickening was noted |
| Kristofik (2017) [118] | Rat thoracic aorta | Allogenic TSP2 KO cells | Yes | 50 µL of cells (at a concentration of 3 × 106 cells/mL) twice | Rat abdominal aorta | 100% at 4 weeks (better than control) | Improved endothelial and mural cell recruitment; Decreased failure rate compared to control grafts |
| Human clinical trial | |||||||
| Olausson (2014) [148] | Human iliac or mammary vein | Autologous ECs and SMCs | Heparin: 50 IU/mL PBS for 2 h | Whole blood: 2 mL/min for 48 h; followed by 4 days EC and 4 days SMC medium perfusion | 2 Pediatric patients (portal veins) | 100% at 21 months in first patients; The second patient received another graft at 7 months (under anticoagulation) | A proof of concept in using tissue engineered vascular graft for clinical patients |
*: Heparin coated vascular graft; #: with G-CSF injection.