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Adult muscle-derived stem cells engraft and differentiate into insulin-expressing cells in pancreatic islets of diabetic mice.

Abstract Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency.
PMID
Related Publications
Authors

Mayor MeshTerms

Cell Differentiation

Maf Transcription Factors, Large

Stem Cell Transplantation

Keywords

Beta-cell differentiation

Insulin secretion

Muscle stem cells

Pancreatic islets

Journal Title stem cell research & therapy
Publication Year Start




PMID- 28420418
OWN - NLM
STAT- MEDLINE
DA  - 20170419
DCOM- 20170508
LR  - 20170508
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 8
IP  - 1
DP  - 2017 Apr 18
TI  - Adult muscle-derived stem cells engraft and differentiate into insulin-expressing
      cells in pancreatic islets of diabetic mice.
PG  - 86
LID - 10.1186/s13287-017-0539-9 [doi]
AB  - BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose 
      homeostasis and their deficiency results in impaired insulin production leading
      to severe diabetic diseases. Here, we investigated the potential of a population 
      of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to
      differentiate in vitro into beta cells when transplanted as undifferentiated stem
      cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured
      MDSC spontaneously differentiated into insulin-expressing islet-like cell
      clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry
      under the control of an insulin promoter. Differentiated clusters of beta-like
      cells co-expressed insulin with the transcription factors Pdx1, Nkx2.2, Nkx6.1,
      and MafA, and secreted significant levels of insulin in response to glucose
      challenges. In vivo, undifferentiated MDSC injected into streptozotocin
      (STZ)-treated mice engrafted within 48 h specifically to damaged pancreatic
      islets and were shown to differentiate and express insulin 10-12 days after
      injection. In addition, injection of MDSC into hyperglycemic diabetic mice
      reduced their blood glucose levels for 2-4 weeks. CONCLUSION: These data show
      that MDSC are capable of differentiating into mature pancreatic beta islet-like
      cells, not only upon culture in vitro, but also in vivo after systemic injection 
      in STZ-induced diabetic mouse models. Being nonteratogenic, MDSC can be used
      directly by systemic injection, and this potential reveals a promising
      alternative avenue in stem cell-based treatment of beta-cell deficiencies.
FAU - Mitutsova, Violeta
AU  - Mitutsova V
AD  - Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille,
      34396, Montpellier cedex 05, France.
FAU - Yeo, Wendy Wai Yeng
AU  - Yeo WWY
AD  - Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille,
      34396, Montpellier cedex 05, France.
AD  - Genetics & Regenerative Medicine Research Centre, Faculty of Medicine and Health 
      Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
FAU - Davaze, Romain
AU  - Davaze R
AD  - Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille,
      34396, Montpellier cedex 05, France.
FAU - Franckhauser, Celine
AU  - Franckhauser C
AD  - Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille,
      34396, Montpellier cedex 05, France.
FAU - Hani, El-Habib
AU  - Hani EH
AD  - Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille,
      34396, Montpellier cedex 05, France.
FAU - Abdullah, Syahril
AU  - Abdullah S
AD  - Genetics & Regenerative Medicine Research Centre, Faculty of Medicine and Health 
      Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
FAU - Mollard, Patrice
AU  - Mollard P
AD  - Networks and Rhythms in Endocrine Glands, IGF, CNRS UMR-5203, Montpellier,
      France.
FAU - Schaeffer, Marie
AU  - Schaeffer M
AD  - Networks and Rhythms in Endocrine Glands, IGF, CNRS UMR-5203, Montpellier,
      France.
FAU - Fernandez, Anne
AU  - Fernandez A
AD  - Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille,
      34396, Montpellier cedex 05, France. [email protected]
FAU - Lamb, Ned J C
AU  - Lamb NJC
AD  - Mammalian Cell Biology group, IGH CNRS, UM, UMR 9002, 141 rue de la Cardonille,
      34396, Montpellier cedex 05, France. [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170418
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Maf Transcription Factors, Large)
RN  - 0 (Trans-Activators)
RN  - 0 (pancreatic and duodenal homeobox 1 protein)
SB  - IM
MH  - Adult Stem Cells/*cytology/metabolism
MH  - Animals
MH  - *Cell Differentiation
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Experimental/*therapy
MH  - Gerbillinae
MH  - Homeodomain Proteins/genetics/metabolism
MH  - Insulin-Secreting Cells/*cytology/metabolism
MH  - *Maf Transcription Factors, Large/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle Fibers, Skeletal/*cytology/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Stem Cell Transplantation
MH  - Trans-Activators/genetics/metabolism
PMC - PMC5395782
OTO - NOTNLM
OT  - Beta-cell differentiation
OT  - Insulin secretion
OT  - Muscle stem cells
OT  - Pancreatic islets
EDAT- 2017/04/20 06:00
MHDA- 2017/05/10 06:00
CRDT- 2017/04/20 06:00
PHST- 2017/02/13 [received]
PHST- 2017/03/16 [accepted]
AID - 10.1186/s13287-017-0539-9 [doi]
AID - 10.1186/s13287-017-0539-9 [pii]
PST - epublish
SO  - Stem Cell Res Ther. 2017 Apr 18;8(1):86. doi: 10.1186/s13287-017-0539-9.

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