Abstract

The spleen is considered a non-essential organ. However, its importance is increasingly clear, given the serious disorders caused by its absence or dysfunction, e.g., greater susceptibility to infections, thromboembolism and cancer. Surgical techniques to preserve the spleen and maintain splenic function have become increasingly common. However, the morbidity and mortality associated with its absence and dysfunction are still high. We used the decellularization technique to obtain a viable splenic scaffold for recellularization in vitro and propose the idea of bioengineered spleen transplantation to the host. We observed the maintenance of important structural components such as white pulp, marginal zone and red pulp, in addition to the network of vascular ducts. The decellularized scaffold presents minimal residual DNA and SDS, which are essential to prevent immunogenic responses and transplantation failure. Also, the main components of the splenic matrix were preserved after decellularization, with retention of approximately 72% in the matrisomal protein content. The scaffold we developed was partially recellularized with stromal cells from the spleen of neonatal rats, demonstrating adhesion, proliferation and viability of cells. Therefore, the splenic scaffold is very promising for use in studies on spleen reconstruction and transplantation, with the aim of complete recovery of splenic function.

Highlights

  • The spleen is a lymphoid organ known to play a role in erythrocyte homeostasis and iron metabolism

  • Its collapse has been demonstrated in cases of Coronavirus Disease 2019 (COVID-19) and experimental model of SARS-CoV-2 infection, where splenic atrophy has been observed, as well as clinical lymphopenia (Chan et al, 2020; Guan et al, 2020; Xu et al, 2020)

  • Histological analysis revealing an absence of cell debris and genetic material (Figures 2a,b). These results were confirmed by the quantification of residual DNA, where a significant reduction in the amount of DNA in the decellularized scaffold was observed when compared to native tissue (4,068 ± 522 vs 51 ± 13 ng/mg dry tissue weight) (Figure 2k)

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Summary

Introduction

The spleen is a lymphoid organ known to play a role in erythrocyte homeostasis and iron metabolism It acts as a filter and in the generation of antigen-specific immune responses that protect the body against blood-borne bacterial, viral and fungal infections (Bronte and Pittet, 2013). Knowing the crucial role of the spleen in the immune response, splenectomy becomes a risk factor for some types of cancer (Mellemkjaer et al, 1995; Kristinsson et al, 2014; Sun et al, 2015). In this setting, surgical techniques to preserve the spleen are becoming increasingly common. Splenosis appears to offer little protection against postsplenectomy infection (Connell et al, 2011)

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