Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function

Taihei Ito, Shin Itakura, Ivan Todorov, Jeffrey Rawson, Sadaki Asari, Jonathan Shintaku, Indu Nair, Kevin Ferreri, Fouad Kandeel, Yoko Mullen

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Abstract

Background. Bone marrow-derived mesenchymal stem cells (MSCs) are known to produce vascular endothelial growth factor. We hypothesize that co-transplantation of MSCs and islets promotes revascularization and improves islet graft function. Methods. Lewis rat islets were infused into the liver of streptozotocin-diabetic syngeneic recipients or transplanted under the renal capsule of nonobese diabetic severe combined immunodeficiency (NOD SCID) mice with MSCs isolated from Lewis bone marrow and expanded in culture. Results. Co-transplantation of 500 islets and 10 MSCs (islet-MSCs) reversed diabetes in all eight recipients, whereas islet-alone transplantation achieved euglycemia in 3 of 10 recipients. With 300 islets, five of nine islet-MSCs and 1 of 10 islets-alone recipients reversed diabetes. Results of intravenous glucose tolerance tests performed on day 56 were significantly better in islet-MSCs than islet-alone recipients. One week after transplantation, well-preserved islet structure and higher number of capillaries were found in the liver of islet-MSCs recipients, whereas islet-alone grafts were fragmented with very few capillaries. Islets showed a similar morphology when transplanted with MSCs in nonobese diabetic severe combined immunodeficiency mice with a significantly higher capillary per β-cell ratio than that in islet-alone grafts (0.135±0.046 vs. 0.052±0.028 capillary segments per β-cell, P<0.01). One week after transplantation, islets were surrounded by MSCs labeled with carboxyfluorescein succinimidyl ester or Qdot nanocrystals, and some labeled MSCs positively stained for vascular endothelial growth factor or von Willebrand factor. Conclusion. Our results demonstrate the improvement of islet graft morphology and function by co-transplantation with MSCs. This improvement is attributable, at least in part, to the promotion of graft revascularization mediated by MSCs.

Original languageEnglish
Pages (from-to)1438-1445
Number of pages8
JournalTransplantation
Volume89
Issue number12
DOIs
Publication statusPublished - 27-06-2010

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Islets of Langerhans Transplantation
Mesenchymal Stromal Cells
Transplants
Mesenchymal Stem Cell Transplantation
Severe Combined Immunodeficiency
Vascular Endothelial Growth Factor A
Bone Marrow
Liver
von Willebrand Factor
Glucose Tolerance Test
Streptozocin
Nanoparticles
Capsules
Esters
Transplantation
Kidney

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Ito, T., Itakura, S., Todorov, I., Rawson, J., Asari, S., Shintaku, J., ... Mullen, Y. (2010). Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function. Transplantation, 89(12), 1438-1445. https://doi.org/10.1097/TP.0b013e3181db09c4
Ito, Taihei ; Itakura, Shin ; Todorov, Ivan ; Rawson, Jeffrey ; Asari, Sadaki ; Shintaku, Jonathan ; Nair, Indu ; Ferreri, Kevin ; Kandeel, Fouad ; Mullen, Yoko. / Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function. In: Transplantation. 2010 ; Vol. 89, No. 12. pp. 1438-1445.
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abstract = "Background. Bone marrow-derived mesenchymal stem cells (MSCs) are known to produce vascular endothelial growth factor. We hypothesize that co-transplantation of MSCs and islets promotes revascularization and improves islet graft function. Methods. Lewis rat islets were infused into the liver of streptozotocin-diabetic syngeneic recipients or transplanted under the renal capsule of nonobese diabetic severe combined immunodeficiency (NOD SCID) mice with MSCs isolated from Lewis bone marrow and expanded in culture. Results. Co-transplantation of 500 islets and 10 MSCs (islet-MSCs) reversed diabetes in all eight recipients, whereas islet-alone transplantation achieved euglycemia in 3 of 10 recipients. With 300 islets, five of nine islet-MSCs and 1 of 10 islets-alone recipients reversed diabetes. Results of intravenous glucose tolerance tests performed on day 56 were significantly better in islet-MSCs than islet-alone recipients. One week after transplantation, well-preserved islet structure and higher number of capillaries were found in the liver of islet-MSCs recipients, whereas islet-alone grafts were fragmented with very few capillaries. Islets showed a similar morphology when transplanted with MSCs in nonobese diabetic severe combined immunodeficiency mice with a significantly higher capillary per β-cell ratio than that in islet-alone grafts (0.135±0.046 vs. 0.052±0.028 capillary segments per β-cell, P<0.01). One week after transplantation, islets were surrounded by MSCs labeled with carboxyfluorescein succinimidyl ester or Qdot nanocrystals, and some labeled MSCs positively stained for vascular endothelial growth factor or von Willebrand factor. Conclusion. Our results demonstrate the improvement of islet graft morphology and function by co-transplantation with MSCs. This improvement is attributable, at least in part, to the promotion of graft revascularization mediated by MSCs.",
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Ito, T, Itakura, S, Todorov, I, Rawson, J, Asari, S, Shintaku, J, Nair, I, Ferreri, K, Kandeel, F & Mullen, Y 2010, 'Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function', Transplantation, vol. 89, no. 12, pp. 1438-1445. https://doi.org/10.1097/TP.0b013e3181db09c4

Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function. / Ito, Taihei; Itakura, Shin; Todorov, Ivan; Rawson, Jeffrey; Asari, Sadaki; Shintaku, Jonathan; Nair, Indu; Ferreri, Kevin; Kandeel, Fouad; Mullen, Yoko.

In: Transplantation, Vol. 89, No. 12, 27.06.2010, p. 1438-1445.

Research output: Contribution to journalArticle

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T1 - Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function

AU - Ito, Taihei

AU - Itakura, Shin

AU - Todorov, Ivan

AU - Rawson, Jeffrey

AU - Asari, Sadaki

AU - Shintaku, Jonathan

AU - Nair, Indu

AU - Ferreri, Kevin

AU - Kandeel, Fouad

AU - Mullen, Yoko

PY - 2010/6/27

Y1 - 2010/6/27

N2 - Background. Bone marrow-derived mesenchymal stem cells (MSCs) are known to produce vascular endothelial growth factor. We hypothesize that co-transplantation of MSCs and islets promotes revascularization and improves islet graft function. Methods. Lewis rat islets were infused into the liver of streptozotocin-diabetic syngeneic recipients or transplanted under the renal capsule of nonobese diabetic severe combined immunodeficiency (NOD SCID) mice with MSCs isolated from Lewis bone marrow and expanded in culture. Results. Co-transplantation of 500 islets and 10 MSCs (islet-MSCs) reversed diabetes in all eight recipients, whereas islet-alone transplantation achieved euglycemia in 3 of 10 recipients. With 300 islets, five of nine islet-MSCs and 1 of 10 islets-alone recipients reversed diabetes. Results of intravenous glucose tolerance tests performed on day 56 were significantly better in islet-MSCs than islet-alone recipients. One week after transplantation, well-preserved islet structure and higher number of capillaries were found in the liver of islet-MSCs recipients, whereas islet-alone grafts were fragmented with very few capillaries. Islets showed a similar morphology when transplanted with MSCs in nonobese diabetic severe combined immunodeficiency mice with a significantly higher capillary per β-cell ratio than that in islet-alone grafts (0.135±0.046 vs. 0.052±0.028 capillary segments per β-cell, P<0.01). One week after transplantation, islets were surrounded by MSCs labeled with carboxyfluorescein succinimidyl ester or Qdot nanocrystals, and some labeled MSCs positively stained for vascular endothelial growth factor or von Willebrand factor. Conclusion. Our results demonstrate the improvement of islet graft morphology and function by co-transplantation with MSCs. This improvement is attributable, at least in part, to the promotion of graft revascularization mediated by MSCs.

AB - Background. Bone marrow-derived mesenchymal stem cells (MSCs) are known to produce vascular endothelial growth factor. We hypothesize that co-transplantation of MSCs and islets promotes revascularization and improves islet graft function. Methods. Lewis rat islets were infused into the liver of streptozotocin-diabetic syngeneic recipients or transplanted under the renal capsule of nonobese diabetic severe combined immunodeficiency (NOD SCID) mice with MSCs isolated from Lewis bone marrow and expanded in culture. Results. Co-transplantation of 500 islets and 10 MSCs (islet-MSCs) reversed diabetes in all eight recipients, whereas islet-alone transplantation achieved euglycemia in 3 of 10 recipients. With 300 islets, five of nine islet-MSCs and 1 of 10 islets-alone recipients reversed diabetes. Results of intravenous glucose tolerance tests performed on day 56 were significantly better in islet-MSCs than islet-alone recipients. One week after transplantation, well-preserved islet structure and higher number of capillaries were found in the liver of islet-MSCs recipients, whereas islet-alone grafts were fragmented with very few capillaries. Islets showed a similar morphology when transplanted with MSCs in nonobese diabetic severe combined immunodeficiency mice with a significantly higher capillary per β-cell ratio than that in islet-alone grafts (0.135±0.046 vs. 0.052±0.028 capillary segments per β-cell, P<0.01). One week after transplantation, islets were surrounded by MSCs labeled with carboxyfluorescein succinimidyl ester or Qdot nanocrystals, and some labeled MSCs positively stained for vascular endothelial growth factor or von Willebrand factor. Conclusion. Our results demonstrate the improvement of islet graft morphology and function by co-transplantation with MSCs. This improvement is attributable, at least in part, to the promotion of graft revascularization mediated by MSCs.

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