Bone Fragment Co-transplantation Alongside Bone Marrow Aspirate Infusion Protects Kidney Transplant Recipients

Abstract

Integration of non-vascularized bone grafting and bone marrow aspirate infusion in transplantation may provide clinical benefit. Here we have incorporated bone fragment co-transplantation and bone marrow aspirate infusion (BF-BM) into living kidney transplantation (LKT). Twenty LKT recipients receiving bone fragments and bone marrow aspirates donated from their corresponding donors were enrolled into a retrospective study. A contemporaneous control group was formed of 38 out of 128 conventional LKT recipients, selected using propensity score matching by a 1:2 Greedy algorithm. Ultrasonography, contrast-enhanced ultrasonography (US/CEUS) and SPECT/CT showed that the co-transplanted bone fragments remained viable for 6 months, subsequently shrank, and finally degenerated 10 months post-transplantation. BF-BM resulted in earlier kidney recovery and more robust long-term kidney function. Throughout 5 years of follow-up, BF-BM had regulatory effects on dendritic cells (DCs), T helper (Th1/Th2) cells and regulatory T cells (Tregs). Both alloantigen-specific lymphocyte proliferation and panel reactive antibody levels were negative in all recipients with or without BF-BM. In addition, the BF-BM group experienced few complications during the 5-year follow-up (as did the donors)-this was not different from the controls. In conclusion, BF-BM is safe and benefits recipients by protecting the kidney and regulating the immune response.

Keywords: bone fragment co-transplantation; bone marrow aspirate infusion; immune regulation; kidney protection; living kidney transplantation (LKT).

Figure 1

Persistence of bone grafts post-transplantation. (A) Bone grafts were detected by ultrasound at 1, 3, 6, and 10 months post-transplantation. The orange circles indicate the ranges for each bone graft. (B) Bone grafts were detected by CT scan at 1, 3, 6, and 10 months post-transplantation. (C) Bone graft CT values were detected by CT scan. (D) Bone graft volumes were detected by CT scan. *p < 0.05; **p < 0.01.

Figure 2

Blood supply analysis of bone grafts. (A) CEUS photography of the bone grafts at 1, 3, 6, and 10 months post-transplantation. (B) Blood supply of bone grafts represented by MBF values at 1, 3, 6, and 10 months post-transplantation.

Figure 3

Metabolic activity of bone grafts. (A) Hybrid SPECT/CT photography of the bone grafts at 1, 3, 6, 10, and 15 months post-transplantation. (B) Metabolic viability of the bone grafts, represented by BMax/NMax values, showing alterations according to the time-point post-transplantation.

Figure 4

Kidney function post-transplantation. (A) Creatinine levels of the recipients throughout the 5-year follow-up. (B) eGFR throughout the 5-year follow-up. **, p < 0.01.

Figure 5

Recipient immune status after transplantation. (A) Proportions of DC, Th1, Th2, CTL, Th17, Treg, MΦ, NK, and NKT in PBMCs at day 0, 6 months, 1 year, 3 years, and 5 years post-transplantation. (B) Serum levels of IL-2, IL-6, TNF-α, IFN-γ, IL-17F, IL-4, IL-6, IL-9, IL-10, and IL-13 at the same time points. Assays were performed in duplicate and each dot represents one replicate. (C) Tacrolimus trough levels at 1, 3, and 5 years post-transplantation. *, p < 0.05; **, p < 0.01.

Figure 6