The spleen—a potential source of new islets for transplantation?

Robertson, Stuart; Rowan-Hull, Autumn M.; Johnson, Paul

doi:10.1016/j.jpedsurg.2007.10.013

Cited by 13 publications

(15 citation statements)

References 25 publications

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“…In disease or injury, splenic stem cells are capable of self-renewal, differentiation, restoration and/or changes in function of a broad range of tissues, e.g., pancreatic islets (Kodama et al, 2003; Robertson et al, 2008; Park et al, 2009; Yin et al, 2006), salivary epithelial cells (Tran et al, 2007), osteoblast-like cells (Macias et al, 2001), cranial neurons (Lonyai et al, 2008a,b), inner ear structures (Lonyai et al, 2008a,b), lymphocytes (Kodama et al, 2003), and more differentiated immune cells (novel dendritic cells and macrophages) that repair damaged heart cells after ischemic injury or extended lymphocyte lineages (Swirski et al, 2009; Tan et al, 2010). In several of these studies, the newly differentiated stem cells contribute to full and stable functional restoration.…”

Section: Introductionmentioning

confidence: 99%

“…The two diseases in the NOD mouse share overlapping pathology as a result of similar genetic and protein abnormalities (Hayashi and Faustman, 1999, 2000). Further, the salivary glands and the pancreas are developmentally related: they derive from the same embryonic region that spawns the spleen (Lonyai et al, 2008b; Kodama et al, 2003, 2005a,b; Robertson et al, 2008; Park et al, 2009; Yin et al, 2006; Ryu et al, 2001; Nishio et al, 2006; Suri et al, 2006). In animals with Sjogren’s syndrome, donor splenocytes both directly and indirectly regenerate the salivary glands (Tran et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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

Faustman

Davis

2010

The International Journal of Biochemistry & Cell Biology

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Faustman

Davis

2010

The International Journal of Biochemistry & Cell Biology

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“…The evidence shows that administration of splenic stem cells, after disease or injury, leads to regeneration of the following tissues: pancreatic islets, osteoblast-like bone cells, T lymphocytes, salivary epithelial cells, and cranial neurons (Kodama et al, 2003, Lonyai et al, 2008, Tran et al, 2007, Macias et al, 2001, Khaldoyanidi et al, 2003, Park et al, 2009, Yin et al, 2006). Splenic stem cells also have been found to regenerate part of the inner ear of deaf mice and can restore hearing after complete deafness in some animals (Lonyai et al, 2008) Splenic stem cells harvested from birds can form insulin-secreting pancreatic islets in vitro (Robertson et al, 2008) similar to in vivo findings in mice with type 1 diabetes (Kodama et al, 2003) and most recently, the spleen serves as a reservoir for immature cells that function in repairing the heart after myocardial infarction(Swirski et al, 2009). …”

Section: Introductionmentioning

confidence: 91%

“…The spleen of several adult species, including humans, contains a population of naturally occurring stem cells with multi-lineage capacities (Macias et al, 2001, Dieguez-Acuna et al, Khaldoyanidi et al, 2003, Kodama et al, 2003, Kodama et al, 2005a, Yin et al, 2006, Tran et al, 2007, Lonyai et al, 2008, Robertson et al, 2008, Swirski et al, 2009, Park et al, 2009). These stem cells are non-lymphoid (CD45-) cells, contrary to the spleen's predominant cell type, CD45+ lymphoid cells.…”

Section: Introductionmentioning

confidence: 99%

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

Dieguez-Acuña

Kodama

Okubo

et al. 2010

The International Journal of Biochemistry & Cell Biology

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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.

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“…The spleen, which is often regarded as a large lymph node, contains lymphocytes and monocytes/macrophages that fight against hazardous events such as infection. However, several studies have reported the existence of specific stem cells whose differentiation capacity is not restricted to hematopoietic cells (Kodama, Kuhtreiber, Fujimura, Dale, & Faustman, ; Macias et al., ; Robertson, Rowan‐Hull, & Johnson, ; Swirski et al., ; Yin et al., ). For example, Faustman et al.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of splenic adherent cells forming densely‐packed colonies

et al. 2019

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It is thought that the spleen contains stem cells that differentiate into somatic cells other than immune cells. We investigated the presence of these hypothetical splenic cells with stem cell characteristics and identified adherent cells forming densely‐packed colonies (Splenic Adherent Colony‐forming Cell; SACC) in the spleen. Splenic Adherent Colony‐forming Cell was positive for alkaline phosphatase staining and stage‐specific embryonic antigen (SSEA)‐1 antigen. However, the self‐renewal properties of SACCs were limited because they stopped cell proliferation once colonies visible to the naked eye were formed. Gene expression analyses by semi‐quantitative RT‐PCR revealed the significant expression of c‐Myc and Klf4, whereas faint or no expression was evident for Nanog, Oct3/4, and Sox2. Global expression analyses by DNA microarray and subsequent gene ontology analyses revealed that the expression levels of genes related to the immune system were significantly lower in SACCs than in control splenic cells. In contrast, genes unrelated to the immune system, such as those involved in cell adhesion and axon guidance, were relatively highly expressed in SACCs compared with control splenic cells. Taken together, we identified a novel cell type residing in the spleen that is different from the hypothetical splenic stem cell, but which bears some, but not all, characteristics that represent an undifferentiated state.

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The spleen—a potential source of new islets for transplantation?

Cited by 13 publications

References 25 publications

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

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

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

Identification and characterization of splenic adherent cells forming densely‐packed colonies

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