Interaction of Cells with Decellularized Biological Materials - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 112

Erdbrügger et al. [ 38 ] published data from a clinical trial involving patients who
had received a decellularized porcine valve replacement. The substitute was
explanted after 10 months because of an aneurysm at the ligature. Histological
analysis on the explant demonstrated endothelial cells on the surface and recolo-
nization of deeper tissue layers with recipient cells. Similar results were reported
by Dohmen et al. [ 48 ] in 2007; however, the patient received a decellularized heart
valve, which had been reseeded in vitro before implantation. The patient was
reoperated on after 3 months. A monolayer of endothelial cells and interstitial cells
was found in deeper tissue layers of the heart valve biopsy.
6 Immunogenicity of Extracellular Matrices
The failure of allogeneic heart valve substitutes may have immunological causes
[ 49 - 54 ]. Basically, the genetic differences of the cellular surface antigens, the
human leukocyte antigen (HLA) molecules, are responsible for immunological
compatibility between donor and recipient. Therefore, incompatibility between
recipient and donor in terms of blood groups (A, B, O) and HLAs may trigger
immunological reactions [ 53 ]. The resulting graft rejection is a host-versus-graft
disease. Use of decellularized tissue may overcome this disadvantage. The cellular
components of the starting material are removed, so the resulting decellularized
tissue mainly consists of an ECM. The elimination of cellular components results
in a reduction of alloreactivity.
In 2005, da Costa et al. [ 55 ] published a study involving 20 patients who
underwent heart valve replacement: 11 patients received decellularized grafts and
nine patients received conventional cryopreserved homografts. The immune status
with regard to the formation of HLA antibodies was collected after 5, 10, 30, 90,
and 180 days. The basal levels in homograft recipients increased 1 month after
surgery and were still elevated 6 months after the surgery. In contrast, no increase
in HLA class I and HLA class II titer was determined in seven patients who
received decellularized grafts. One patient showed a slight increase of HLA class I
levels and two additional patients exhibited an abnormal increase (Fig. 2 ).
The human, pulmonary, decellularized, and cryopreserved CryoValve SG heart
valve from CryoLife has been available on the market sine 2000. CryoValve SG
valves are already in clinical use and publications have report a lower alloreactivity
compared with conventional vital homografts. Several groups have shown that HLA
antibody levels after CryoValve SG implantation were significantly reduced.
Working groups based around Zehr [ 56 ] and Elkins [ 57 ] reported that the CryoValve
SG valve was tolerated by most patients (91%): after 1 month 86% were HLA neg-
ative, 88% were HLA negative after 3 months, and 95% were HLA negative after
1 year. By contrast, HLA immunogenicity of cryopreserved homografts is much
higher. In studies involving pediatric patients (n = 9), Shaddy et al. [ 52 ] demonstrated
an average increase in HLA class I level of 3.2% before surgery to 63% 25 days after
surgery and to 99.7% 3 months after the operation. Further analysis showed that these
antibody levels persisted at a level of about 87% for up to 1 year after surgery.