Regenerative medicine: a radical reappraisal of the spleen (original) (raw)

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

2018

In this review, we show the unique potential of spleen as an optimal site for islet transplantation and a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets. The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic. Spleen also ha...

Disposable No Longer: The Spleen Holds a Reservoir of Stem Cells

Journal of Stem Cell Research & Therapy, 2014

The expression of Hox11 marks splenic stem cells as being embryonic in nature. Hox11 (also known as Tlx1 or TCL-3), initially a protein exclusive to fetal development, was first identified in adult mammals in association with cancers, including T-cell acute lymphocytic leukemia [17]. More research uncovered its fundamental role in development:

Proteomics identifies multipotent and low oncogenic risk stem cells of the spleen

International Journal of Biochemistry & Cell Biology, 2010

The adult spleen harbors a population of naturally occurring multipotent stem cells of non-lymphoid lineage (CD45−). In animal models, these splenic stem cells can directly or indirectly contribute to regeneration of bone, inner ear, cranial nerves, islets, hearts and salivary glands. Here we characterize the CD45− stem cell proteome to determine its potential broader multipotency versus its protection from malignant transformation. Using state-of-the-art proteomics and in vivo testing, we performed functional analyses of unique proteins of CD45− (non-lymphoid) splenic stem cells, as compared with CD45+ (lymphoid) cells. CD45− stem cell-specific proteins were identical to those in iPS, including OCT3/4, SOX2, KLF4, c-MYC and NANOG. They also expressed Hox11, Gli3, Wnt2, and Adam12, the benchmark transcription factors of embryonic stem cells. These transcription factors were functional because their mRNA was upregulated in the spleen in association with ongoing damage to the pancreas and salivary glands, organs to which they normally contribute stem cells. We also show low likelihood of malignant transformation. Our proteomic and functional analyses reveals that naturally occurring CD45− stem cells of the spleen are the first-ever candidates for naturally occurring population of embryonic and iPS cells with low oncogenic risk. Given their presence in normal humans and mice, splenic stem cells are poised for translational research.

Telomerase-Positive Stem Cells in Adult Porcine and Adult Rat Spleens I. Totipotent Stem Cells

Journal of Regenerative Medicine & Biology Research, 2020

Previous studies have reported the presence of endogenous undifferentiated totipotent stem cells within the organs and tissues of various animal species, including the spleen. Since one major function of the spleen is to filter out damaged red blood cells, we wanted to ascertain whether totipotent stem cells existed as a potentially transient circulating population solely within the vasculature and sinusoids of the spleen or whether they existed as an endogenous resident population of primitive stem cells throughout the tissues of the spleen, and potentially involved in the repair of the spleen. The spleens from two separate mammalian species were examined, i.e., adult pigs and adult rats. Adult pigs were euthanized following the guidelines of Fort Valley State University’s IACUC. Adult rats were euthanized following the guidelines of Mercer University School of Medicine’s IACUC. The spleens were harvested, fixed, frozen, cryosectioned, and stained with an antibody diagnostic for the endogenous totipotent stem cells, i.e., Carcinoembryonic Antigen-Cell Adhesion Molecule-1 (CEA-CAM-1). CEA-CAM-1 positive stem cells were located within the capsule of the spleen, along the splenic trabeculae, within the red pulp, within the white pulp, along the central arteries and surrounding the penicillar arteries of the spleen in both the adult pig and in the adult rat. These results suggested that the totipotent stem cells are a resident population of stem cells within the splenic tissues. Studies are ongoing to address their functional significance in repair of the spleen.

The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice

PloS one, 2017

Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP). The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those imme...

Stem cells in the adult pancreas and liver

2007

Stem cells are undifferentiated cells that can self-renew and generate specialized (functional) cell types. The remarkable ability of stem cells to differentiate towards functional cells makes them suitable modalities in cellular therapy (which means treating diseases with the body's own cells). Potential targets for cellular therapy include diabetes and liver failure. However, in order for stem cells to be clinically useful, we must learn to identify them and to regulate their differentiation. We will use the intestine as a classical example of a stem cell compartment, and then examine the evidence for the existence of adult stem cells in two endodermally derived organs: pancreas and liver. We will review the characteristics of the putative stem cells in these tissues and the transcription factors controlling their differentiation towards functional cell types.

Stem cells: an alternative to organ transplantation

Even in the absence of damage or illness mature animals need billions of new cells every single day of their lives in order to survive and renew circulating blood cells and intestinal and skin lining. This task is accomplished by undifferentiated cells residing in most adult organs. These cells are designated adult stem cells (ASC) since they represent the adult counterpart, present in almost every organ, of the embryonal stem cells (ES) from which the entire human body develops. Scientists first hypothesized the existence of stem cells over a century ago, and haematopoietic stem cells (HSC) have been exploited for the therapy of human diseases for two decades. Other types of stem cells also circulating in the bloodstream have been described. We briefly describe the potential uses of each of these types of cells, including autologous circulating stem cells, for disease therapy and in particular for the possible reversal of liver failure due to chronic hepatitis and/or cirrhosis.