Stem cells in the spleen: Therapeutic potential for Sjogren's syndrome, type I diabetes, and other disorders

Abstract

The view of the spleen as an unnecessary organ has been shattered. The evidence shows the spleen to be a source of naturally-occurring multipotent stem cells with possibly pluripotent potential. The stem cells are sequestered in the spleen of not only of animals but also of normal human adults. The reservoir of cells is set for differentiation and they need not be manipulated in vitro or ex vivo before autologous or heterologous use. Splenic stem cells, of Hox11 lineage, have been found in disease or injury to differentiate into pancreatic islets, salivary epithelial cells and osteoblast-like cells, cranial neurons, cochlea, lymphocytes, and more differentiated immune cells that repair injured heart cells. Injury or disease in target tissues induces these stem cells, still in the spleen, to upregulate the same embryonic transcription factors artificially introduced into induced pluripotent stem cells (iPS). Splenic stem cells may have broad pluripotent potential, but unlike iPS cells, possess low oncogenic risk.

Thrombospondin-1 Signaling through CD47 Inhibits Self-renewal by Regulating c-Myc and Other Stem Cell Transcription Factors

“…The spleen of adult mice contains a pool of multipotent CD45 − /Hox11 + stem cells that reside in the sub-capsular red pulp and are capable of differentiating into diverse lineages4647. Consistent with these reports, we observed a limited number of cells with nuclear Sox2 protein expression in the sub-capsular region of WT mouse spleen (Fig.…”

Mesenchymal Stromal Cells Improve Salivary Function and Reduce Lymphocytic Infiltrates in Mice with Sjögren's-Like Disease

“…We concluded that CFA was insufficient to decrease the inflammatory cell infiltrates in SGs and started to investigate for additional approaches to our proposed combined therapy. Recent evidence from our collaborators (DL Faustman and S Kodama) indicated that multipotent stem cells of non-lymphoid lineage (CD45-negative; CD45 − ) from the spleen contributed to the regeneration of bone, inner ear, cranial nerves, islets, hearts, and of particular interest to our work, salivary glands [12], [13], [14], [15]. The spleen and bone marrow are closely related organs, and both are among the first sites of hematopoiesis during gestation.…”

Effect of Subconjunctival Lacrimal Gland Transplantation in a Rabbit Dry Eye Model

“…5,6 However, these drugs cannot promote tear secretion from the lacrimal gland, so the application of lacrimal glandregenerative techniques, such as stem cell transplantation or induction of induced pluripotent stem cells, may be essential to increase tear volume. [7][8][9] Currently, these techniques have not been clinically approved for use.…”