## 3 Clinical Study in Venous Model
While the original tissue engineering paradigms believed that cells seeded onto a scaffold would eventually constitute the neotissue, we found this not to be the case. We found that host-macrophage infiltration is essential for vascular neotissue formation, while excessive infiltration underlies stenosis. Our findings suggested that achieving the proper balance of macrophage infiltration and function is critical for successful neoessel formation [65]. Subsequently, we have continued to investigate the effect of seeding bone marrow-derived mononuclear cells on TEVGs in lambs, as the ovine model is preferred by the FDA due to its propensity to undergo accelerated calcification. As previously mentioned, when we began our original large animal studies in the late 1990s, we expanded cells from an explanted vein, a process that would take anywhere from 8 to 12 weeks [66]. Cell expansion is a time-consuming and costly process. Additionally, cultured cells are susceptible to infection. Being able to utilize bone marrow as a cell source cut a process that required two separate surgeries over the course of a few months to one procedure that \begin{table}
\begin{tabular}{c c c c c} \hline
**Patient** & **Main Diagnosis** & **Age** & **Graft Type** & **Graft Size** \\ \hline
1 & Asplenia, AVSD(A), small RV & 2 & PLA & 16 \\
2 & Asplenia, SRV, TAPVC(lb+III) & 1 & PLA & 20 \\
3 & Concordant criss-cross heart, DORV, PAA, MS & 8 & PLA & 18 \\
4 & TA(lb) & 22 & PLA & 24 \\
5 & PPA, ASD(II), sinusoidal communication & 13 & PLA & 22 \\
6 & SRV, DORV, AVVA & 4 & PLA & 20 \\
7 & Total sinus defect, ASD, TR(IV) & 14 & PLA & 24 \\
8 & Asplenia, SLV, CAVVR & 17 & PLA & 24 \\
9 & TA(lb) & 22 & PLA & 22 \\
10 & Polysplenia, SRV & 4 & PLA & 12 \\
11 & HLHS, MA, IAA(A) & 2 & PLA & 16 \\
12 & Asplenia, SRV, PAA, non-confluent PA & 2 & PGA & 16 \\
13 & SLV, It AVVA & 2 & PGA & 16 \\
14 & DORV, small LV, VSD, PS, ASD(II) & 2 & PGA & 18 \\
15 & polysplenia, cAVSD, DORV, PS & 2 & PGA & 12 \\
16 & Asplenia, SRV, CA, TAPVC(lb) & 2 & PGA & 16 \\
17 & PPA, RA thrombosis, AFL, af & 24 & PGA & 18 \\
18 & SRV, DIRV, PA, ASD(II) & 1 & PGA & 16 \\
19 & Asplenia, SRV, PS, CA & 11 & PGA & 18 \\
20 & polysplenia, cAVSD, PS, CAVVR & 2 & PGA & 14 \\
21 & DORV, VSD, small RV, PLSVC, TAPVC(IIb) & 3 & PGA & 16 \\
22 & PPA, ASD(II), PS, Sinusoidal communication & 5 & PGA & 18 \\
23 & SLV, DILV, PA, ASD, bilateral SVC & 4 & PGA & 18 \\
24 & Asplenia, SRV & 13 & PGA & 16 \\
25 & TA(IIc), SAS & 2 & PGA & 18 \\ \hline \end{tabular} a  
\end{table} 
Table 1: Characteristics of the patients. could be completed in a day. We are developing a closed, disposable system which will allow for improved seeding efficiency and reduce the risk of infection [67]. In regards to the development of graft stenosis, our focus is aimed at modulating the macrophage response. To date, we have shown that pharmacological treatment with a Tgfbr1 inhibitor prevents macrophage induced stenosis and future studies will look at the ability of losartan, an angiotensin II receptor blocker, to mitigate the formation of graft stenosis [68]. Figure 3: Postoperative and late-term TEVG angiography. (**A**) Postoperative angiography in patient 22. (**B**) Angiography 11 years after implantation in patient 22. (**C**) Postoperative angiography in patient 23. (**D**) Angiography eight years after implantation in patient 23. Arrows indicate the TEVG location. Angiography shows macroscopic growth of the TEVGs. Adopted with permission from [PERSON] et al.