Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice

Kado, Takeshi; Tomimaru, Yoshito; Kobayashi, Shogo; Harada, Akima; Sasaki, Kazuki; Iwagami, Yoshifumi; Yamada, Daisaku; Noda, Takehiro; Takahashi, Hidenori; Kita, Shunbun; Shimomura, Iichiro; Miyagawa, Shigeru; Doki, Yuichiro; Eguchi, Hidetoshi

doi:https://doi.org/10.1155/2024/5574968

Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice

Kado, Takeshi; Tomimaru, Yoshito; Kobayashi, Shogo et al.

Journal of Diabetes Research, 2024, 2024(1), 5574968

Number of Access:2,430（2025-07-18 09:59 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97136

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Title	Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice
Creator	NRID 1000070911999 1000070911999 CreatorName Kado, Takeshi
	NRID 1000070528570 1000070528570 researchmap permalink yoshitotomimaru yoshitotomimaru Scopus Author ID 10240341100 10240341100 CreatorName Tomimaru, Yoshito
	NRID 1000030452436 1000030452436 researchmap permalink 30452436 30452436 Scopus Author ID 7405376089 7405376089 ORCID 0000-0002-8828-1067 0000-0002-8828-1067 CreatorName Kobayashi, Shogo
	NRID 1000070535426 1000070535426 CreatorName Harada, Akima
	NRID 1000020745442 1000020745442 researchmap permalink Kazuki_Sasaki Kazuki_Sasaki Scopus Author ID 56087041900 56087041900 CreatorName Sasaki, Kazuki
	NRID 1000060597441 1000060597441 researchmap permalink yiwagami yiwagami Scopus Author ID 35074034100 35074034100 CreatorName Iwagami, Yoshifumi
	NRID 1000060571396 1000060571396 ORCID 0000-0002-6702-3800 0000-0002-6702-3800 researchmap permalink dyamada79222 dyamada79222 Scopus Author ID 37008067700 37008067700 CreatorName Yamada, Daisaku
	NRID 1000050528594 1000050528594 researchmap permalink t-noda t-noda Scopus Author ID 12764559600 12764559600 ORCID 0000-0002-6768-5783 0000-0002-6768-5783 CreatorName Noda, Takehiro
	NRID 1000090601120 1000090601120 ORCID 0000-0003-4801-3540 0000-0003-4801-3540 researchmap permalink hdnr_tkhs hdnr_tkhs Scopus Author ID 7405468781 7405468781 CreatorName Takahashi, Hidenori
	NRID 1000010746572 1000010746572 ORCID 0000-0002-8937-0053 0000-0002-8937-0053 researchmap permalink Shunbun_Kita Shunbun_Kita Scopus Author ID 36873116500 36873116500 CreatorName Kita, Shunbun
	NRID 1000060346145 1000060346145 researchmap permalink shimomura_i shimomura_i Scopus Author ID 7006715546 7006715546 ORCID 0000-0002-0851-9603 0000-0002-0851-9603 CreatorName Shimomura, Iichiro
	NRID 1000070544237 1000070544237 ORCID 0000-0003-0015-6569 0000-0003-0015-6569 researchmap permalink s-miyagawa3154 s-miyagawa3154 Scopus Author ID 55560624700 55560624700 CreatorName Miyagawa, Shigeru
	NRID 1000020291445 1000020291445 researchmap permalink ydoki3251 ydoki3251 Scopus Author ID 7006390687 7006390687 CreatorName Doki, Yuichiro
	NRID 1000090542118 1000090542118 researchmap permalink abcdabcdabcd abcdabcdabcd Scopus Author ID 7101627772 7101627772 CreatorName Eguchi, Hidetoshi
Description	Kado T., Tomimaru Y., Kobayashi S., et al. Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice. Journal of Diabetes Research 2024, 5574968 (2024); https://doi.org/10.1155/2024/5574968.
Abstract	Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1α (SDF-1α)), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: "indirect effects"mediated by angiogenesis and "direct effects"of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes.
Publisher	John Wiley and Sons Inc
Source Title	Journal of Diabetes Research
Volume (Issue)	2024(1)
Page	5574968
Date of Issued	2024-05-17
Language	English
Handle URL	https://hdl.handle.net/11094/97136
PISSN	23146745
eISSN	23146753
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1155/2024/5574968
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Journal of Diabetes Research. 2024, 2024(1), p. 5574968
DC.title	Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice
DC.creator	Kado, Takeshi
	Tomimaru, Yoshito
	Kobayashi, Shogo
	Harada, Akima
	Sasaki, Kazuki
	Iwagami, Yoshifumi
	Yamada, Daisaku
	Noda, Takehiro
	Takahashi, Hidenori
	Kita, Shunbun
	Shimomura, Iichiro
	Miyagawa, Shigeru
	Doki, Yuichiro
	Eguchi, Hidetoshi
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-05-17
DC.identifier	https://doi.org/10.1155/2024/5574968
DC.description	Kado T., Tomimaru Y., Kobayashi S., et al. Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice. Journal of Diabetes Research 2024, 5574968 (2024); https://doi.org/10.1155/2024/5574968.
DCTERMS.abstract	Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1α (SDF-1α)), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: "indirect effects"mediated by angiogenesis and "direct effects"of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	97136
citation_title	Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice
citation_author	Kado, Takeshi
	Tomimaru, Yoshito
	Kobayashi, Shogo
	Harada, Akima
	Sasaki, Kazuki
	Iwagami, Yoshifumi
	Yamada, Daisaku
	Noda, Takehiro
	Takahashi, Hidenori
	Kita, Shunbun
	Shimomura, Iichiro
	Miyagawa, Shigeru
	Doki, Yuichiro
	Eguchi, Hidetoshi
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2024-05-17
citation_journal_title	Journal of Diabetes Research
citation_volume	2024
citation_issue	1
citation_firstpage	5574968
citation_doi	https://doi.org/10.1155/2024/5574968
citation_public_url	https://hdl.handle.net/11094/97136

Skeletal Myoblast Cells Enhance the Function of Transplanted Islets in Diabetic Mice

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