The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells

Abstract

This review demonstrates the unique potential of the spleen as an optimal site for islet transplantation and as a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy used to treat severe diabetes mellitus; however, its clinical outcome is currently unsatisfactory. Selection of the most appropriate transplantation site is a major factor affecting the clinical success of this therapy. The spleen has long been studied as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity, and it has recently also been shown to contribute to the regeneration of transplanted islets. However, the efficacy of transplantation in the spleen is lower than that of intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established to allow the spleen to be used for clinical transplantation. The spleen is also of interest as a mesenchymal stem cell reservoir. Splenic mesenchymal stem cells contribute to the repair of damaged tissue, and their infusion may thus be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

Comparative Study of Two Different Islet Transplantation Sites in Mice: Hepatic Sinus Tract vs Splenic Parenchyma

“…Previous studies have suggested that the graft is more likely to be rejected by the recipient when it directly contacts with lymphoid tissue or organs such as spleen, and on the other hand, no special advantages of islet grafts in the SP over the liver were found 26 , 27 . However, recent studies 14 , 15 have found that intrasplenic islet transplantation requires less marginal islet mass (50 syngeneic islets) than the portal vein and subrenal capsule route, suggesting that the spleen may have a better survival environment for islet grafts. In other words, the efficiency of intrasplenic islet transplantation remains controversial 28 – 30 .…”

“…First, the spleen favors the expansion of the islet graft 14 . Secondly, the spleen acts as a stem cell reservoir, which accelerates the repair of the damage caused by the transplantation procedure 15 . Furthermore, it has been reported that these splenic mesenchymal stem cells may differentiate directly into islets 31 .…”

“…In the previous study 13 , our team successfully established a model of islet transplantation in the hepatic sinus tract (HST), and achieved a therapeutic effect comparable to that of subrenal islet transplantation. Recent studies have reported that the spleen is an ideal islet transplantation site due to its reduced inflammation and expansion of the islet graft 14 , 15 . However, we have no idea of which islet transplantation site is better between the HST and SP.…”

Kidney‐in‐a‐lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates

“…Renal subcapsular transplantation of kidney organoids has been exploited to induce neo‐vasculogenesis (van den Berg et al, ), but this approach suffers from poor clinical translatability as the inflammatory and fibrotic milieu of a chronically injured kidney might not support the engraftment, survival, and function of the transplanted cells. In addition, clinical progress in renal subcapsular transplantation has lagged behind other techniques due to the inelastic and tight nature of the human renal subcapsular space (Sakata, Yoshimatsu, & Kodama, ).…”

Regenerative and Transplantation Medicine: Cellular Therapy Using Adipose Tissue-Derived Mesenchymal Stromal Cells for Type 1 Diabetes Mellitus

“…Another possible therapy is islet transplantation, a type of cellular replacement therapy that can rescue the production of an appropriate amount of insulin in a glucose-dependent manner and thereby diminish the risk of hypoglycemia [12,13]. This therapy would also enable patients to be free from the need to administer insulin [14,15]. However, compared with pancreas whole organ transplantation, islet transplantation has poor efficacy.…”