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Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice.

Himeno T, Kamiya H, Naruse K, Cheng Z, Ito S, Shibata T, Kondo M, Kato J, Okawa T, Fujiya A, Suzuki H, Kito T, Hamada Y, Oiso Y, Isobe K, Nakamura J - J Diabetes Res (2015)

Bottom Line: However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects.Transplanted cells maintained their viabilities and differentiated to endothelial cells and smooth muscle cells around the injection sites.Moreover, several transplanted cells constructed chimeric blood vessels with recipient cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan ; Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

ABSTRACT

Background: Although numerous reports addressing pathological involvements of diabetic polyneuropathy have been conducted, a universally effective treatment of diabetic polyneuropathy has not yet been established. Recently, regenerative medicine studies in diabetic polyneuropathy using somatic stem/progenitor cell have been reported. However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects. Here, we investigated the efficacy of treatment for diabetic polyneuropathy using angioblast-like cells derived from mouse embryonic stem cells.

Methods and results: Angioblast-like cells were obtained from mouse embryonic stem cells and transplantation of these cells improved several physiological impairments in diabetic polyneuropathy: hypoalgesia, delayed nerve conduction velocities, and reduced blood flow in sciatic nerve and plantar skin. Furthermore, pathologically, the capillary number to muscle fiber ratios were increased in skeletal muscles of transplanted hindlimbs, and intraepidermal nerve fiber densities were ameliorated in transplanted plantar skin. Transplanted cells maintained their viabilities and differentiated to endothelial cells and smooth muscle cells around the injection sites. Moreover, several transplanted cells constructed chimeric blood vessels with recipient cells.

Conclusions: These results suggest that transplantation of angioblast like cells induced from embryonic stem cells appears to be a novel therapeutic strategy for diabetic polyneuropathy.

No MeSH data available.


Related in: MedlinePlus

Tube forming assay of angioblast-like cells induced from ES cells (ES-ABs) on Matrigel. To elucidate whether ES-ABs themselves are enabled to form blood vessels, sorted ES-ABs and Flk1 negative cells were, respectively, seeded on Matrigel. Two days later, cells were visualized with isolectin IB4, a stain of endothelial cell. (a) Although endothelial cells stained with IB4 were rarely induced from Flk1 negative cells (right), heavy numbers of endothelial cells were induced from ES-ABs and deployed cobblestone-like pattern (left). Bar: 100 μm. Red: isolectin IB4. (b) In ES-AB culture, a part of cells stained with IB4 structured vessel like tube formation (left 2 images). On the other hand, cells forming a line were not stained with IB4 in culture of Flk1 negative cells (right 2 images). Bar: 100 μm. Red: isolectin IB4 and blue: DAPI.
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fig4: Tube forming assay of angioblast-like cells induced from ES cells (ES-ABs) on Matrigel. To elucidate whether ES-ABs themselves are enabled to form blood vessels, sorted ES-ABs and Flk1 negative cells were, respectively, seeded on Matrigel. Two days later, cells were visualized with isolectin IB4, a stain of endothelial cell. (a) Although endothelial cells stained with IB4 were rarely induced from Flk1 negative cells (right), heavy numbers of endothelial cells were induced from ES-ABs and deployed cobblestone-like pattern (left). Bar: 100 μm. Red: isolectin IB4. (b) In ES-AB culture, a part of cells stained with IB4 structured vessel like tube formation (left 2 images). On the other hand, cells forming a line were not stained with IB4 in culture of Flk1 negative cells (right 2 images). Bar: 100 μm. Red: isolectin IB4 and blue: DAPI.

Mentions: To elucidate whether ES-ABs themselves are enabled to form blood vessels, sorted ES-AB and Flk1− cells were separately seeded on Matrigel. After culturing for 2 days on Matrigel, cells were visualized with isolectin IB4. Although endothelial cells stained with IB4 were rarely induced from Flk1− cells, significantly heavy numbers of endothelial cells were induced from Flk1+ cells. In addition, a portion of these endothelial cells restructured into a vessel-like tube formation, and the remaining portion deployed into a cobblestone-like configuration (Figures 4(a) and 4(b)).


Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice.

Himeno T, Kamiya H, Naruse K, Cheng Z, Ito S, Shibata T, Kondo M, Kato J, Okawa T, Fujiya A, Suzuki H, Kito T, Hamada Y, Oiso Y, Isobe K, Nakamura J - J Diabetes Res (2015)

Tube forming assay of angioblast-like cells induced from ES cells (ES-ABs) on Matrigel. To elucidate whether ES-ABs themselves are enabled to form blood vessels, sorted ES-ABs and Flk1 negative cells were, respectively, seeded on Matrigel. Two days later, cells were visualized with isolectin IB4, a stain of endothelial cell. (a) Although endothelial cells stained with IB4 were rarely induced from Flk1 negative cells (right), heavy numbers of endothelial cells were induced from ES-ABs and deployed cobblestone-like pattern (left). Bar: 100 μm. Red: isolectin IB4. (b) In ES-AB culture, a part of cells stained with IB4 structured vessel like tube formation (left 2 images). On the other hand, cells forming a line were not stained with IB4 in culture of Flk1 negative cells (right 2 images). Bar: 100 μm. Red: isolectin IB4 and blue: DAPI.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4419216&req=5

fig4: Tube forming assay of angioblast-like cells induced from ES cells (ES-ABs) on Matrigel. To elucidate whether ES-ABs themselves are enabled to form blood vessels, sorted ES-ABs and Flk1 negative cells were, respectively, seeded on Matrigel. Two days later, cells were visualized with isolectin IB4, a stain of endothelial cell. (a) Although endothelial cells stained with IB4 were rarely induced from Flk1 negative cells (right), heavy numbers of endothelial cells were induced from ES-ABs and deployed cobblestone-like pattern (left). Bar: 100 μm. Red: isolectin IB4. (b) In ES-AB culture, a part of cells stained with IB4 structured vessel like tube formation (left 2 images). On the other hand, cells forming a line were not stained with IB4 in culture of Flk1 negative cells (right 2 images). Bar: 100 μm. Red: isolectin IB4 and blue: DAPI.
Mentions: To elucidate whether ES-ABs themselves are enabled to form blood vessels, sorted ES-AB and Flk1− cells were separately seeded on Matrigel. After culturing for 2 days on Matrigel, cells were visualized with isolectin IB4. Although endothelial cells stained with IB4 were rarely induced from Flk1− cells, significantly heavy numbers of endothelial cells were induced from Flk1+ cells. In addition, a portion of these endothelial cells restructured into a vessel-like tube formation, and the remaining portion deployed into a cobblestone-like configuration (Figures 4(a) and 4(b)).

Bottom Line: However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects.Transplanted cells maintained their viabilities and differentiated to endothelial cells and smooth muscle cells around the injection sites.Moreover, several transplanted cells constructed chimeric blood vessels with recipient cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan ; Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

ABSTRACT

Background: Although numerous reports addressing pathological involvements of diabetic polyneuropathy have been conducted, a universally effective treatment of diabetic polyneuropathy has not yet been established. Recently, regenerative medicine studies in diabetic polyneuropathy using somatic stem/progenitor cell have been reported. However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects. Here, we investigated the efficacy of treatment for diabetic polyneuropathy using angioblast-like cells derived from mouse embryonic stem cells.

Methods and results: Angioblast-like cells were obtained from mouse embryonic stem cells and transplantation of these cells improved several physiological impairments in diabetic polyneuropathy: hypoalgesia, delayed nerve conduction velocities, and reduced blood flow in sciatic nerve and plantar skin. Furthermore, pathologically, the capillary number to muscle fiber ratios were increased in skeletal muscles of transplanted hindlimbs, and intraepidermal nerve fiber densities were ameliorated in transplanted plantar skin. Transplanted cells maintained their viabilities and differentiated to endothelial cells and smooth muscle cells around the injection sites. Moreover, several transplanted cells constructed chimeric blood vessels with recipient cells.

Conclusions: These results suggest that transplantation of angioblast like cells induced from embryonic stem cells appears to be a novel therapeutic strategy for diabetic polyneuropathy.

No MeSH data available.


Related in: MedlinePlus