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Engineering human stellate cells for beta cell replacement therapy promotes in vivo recruitment of regulatory T cells

Oran, D. C.; Lokumcu, T.; Inceoglu, Y.; Akolpoglu, M. B.; Albayrak, O.; Bal, T.; Kurtoglu, M.; Erkan, M.; Can, F.; Bagci-Onder, T.; Kizilel, S.


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{
  "DOI": "10.1016/j.mtbio.2019.100006", 
  "abstract": "Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic beta cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients' own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward the implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance.", 
  "author": [
    {
      "family": "Oran", 
      "given": " D. C."
    }, 
    {
      "family": "Lokumcu", 
      "given": " T."
    }, 
    {
      "family": "Inceoglu", 
      "given": " Y."
    }, 
    {
      "family": "Akolpoglu", 
      "given": " M. B."
    }, 
    {
      "family": "Albayrak", 
      "given": " O."
    }, 
    {
      "family": "Bal", 
      "given": " T."
    }, 
    {
      "family": "Kurtoglu", 
      "given": " M."
    }, 
    {
      "family": "Erkan", 
      "given": " M."
    }, 
    {
      "family": "Can", 
      "given": " F."
    }, 
    {
      "family": "Bagci-Onder", 
      "given": " T."
    }, 
    {
      "family": "Kizilel", 
      "given": " S."
    }
  ], 
  "container_title": "MATERIALS TODAY BIO", 
  "id": "71561", 
  "issued": {
    "date-parts": [
      [
        2019, 
        1, 
        1
      ]
    ]
  }, 
  "title": "Engineering human stellate cells for beta cell replacement therapy promotes in vivo recruitment of regulatory T cells", 
  "type": "article-journal", 
  "volume": "2"
}
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