Gestational age-dependent increase of survival motor neuron protein in umbilical cord-derived mesenchymal stem cells

Sota Iwatani, Nur Imma Fatimah Harahap, Dian Kesumapramudya Nurputra, Shinya Tairaku, Akemi Shono, Daisuke Kurokawa, Keiji Yamana, Khin Kyae Mon Thwin, Makiko Yoshida, Masami Mizobuchi, Tsubasa Koda, Kazumichi Fujioka, Mariko Ikeda, Hideto Yamada, Ichiro Morioka, Kazumoto Iijima, Hisahide Nishio, Noriyuki Nishimura

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Spinal muscular atrophy (SMA) is the most common genetic neurological disease leading to infant death. It is caused by loss of survival motor neuron (SMN) 1 gene and subsequent reduction of SMN protein in motor neurons. Because SMN is ubiquitously expressed and functionally linked to general RNA metabolism pathway, fibroblasts (FBs) are most widely used for the assessment of SMN expression in SMA patients but usually isolated from skin biopsy samples after the onset of overt symptoms. Although recent translational studies of SMN-targeted therapies have revealed the very limited time window for effective SMA therapies during perinatal period, the exact time point when SMN shortage became evident is unknown in human samples. In this study, we analyzed SMN mRNA and protein expression during perinatal period by using umbilical cord-derived mesenchymal stem cells (UC-MSCs) obtained from preterm and term infants. Methods: UC-MSCs were isolated from 16 control infants delivered at 22-40 weeks of gestation and SMA fetus aborted at 19 weeks of gestation (UC-MSC-Control and UC-MSC-SMA). FBs were isolated from control volunteer and SMA patient (FB-Control and FB-SMA). SMN mRNA and protein expression in UC-MSCs and FBs was determined by RT-qPCR and Western blot. Results: UC-MSC-Control and UC-MSC-SMA expressed the comparable level of MSC markers on their cell surface and were able to differentiate into adipocytes, osteocytes, and chondrocytes. At steady state, SMN mRNA and protein expression was decreased in UC-MSC-SMA compared to UC-MSC-Control, as observed in FB-SMA and FB-Control. In response to histone deacetylase inhibitor valproic acid, SMN mRNA and protein expression in UC-MSC-SMA and FB-SMA was increased. During perinatal development from 22 to 40 weeks of gestation, SMN mRNA and protein expression in UC-MSC-Control was positively correlated with gestational age. Conclusion: UC-MSCs isolated from 17 fetus/infant of 19-40 weeks of gestation are expressed functional SMN mRNA and protein. SMN mRNA and protein expression in UC-MSCs is increased with gestational age during perinatal development.

Original languageEnglish
Article number194
JournalFrontiers in Pediatrics
Volume5
DOIs
Publication statusPublished - 05-09-2017

Fingerprint

Umbilical Cord
Spinal Muscular Atrophy
Motor Neurons
Mesenchymal Stromal Cells
Gestational Age
Fibroblasts
Proteins
Messenger RNA
Pregnancy
Aborted Fetus
Osteocytes
Inborn Genetic Diseases
Histone Deacetylase Inhibitors
Valproic Acid
Chondrocytes
Adipocytes
Premature Infants
Volunteers
Fetus

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Iwatani, S., Harahap, N. I. F., Nurputra, D. K., Tairaku, S., Shono, A., Kurokawa, D., ... Nishimura, N. (2017). Gestational age-dependent increase of survival motor neuron protein in umbilical cord-derived mesenchymal stem cells. Frontiers in Pediatrics, 5, [194]. https://doi.org/10.3389/fped.2017.00194
Iwatani, Sota ; Harahap, Nur Imma Fatimah ; Nurputra, Dian Kesumapramudya ; Tairaku, Shinya ; Shono, Akemi ; Kurokawa, Daisuke ; Yamana, Keiji ; Thwin, Khin Kyae Mon ; Yoshida, Makiko ; Mizobuchi, Masami ; Koda, Tsubasa ; Fujioka, Kazumichi ; Ikeda, Mariko ; Yamada, Hideto ; Morioka, Ichiro ; Iijima, Kazumoto ; Nishio, Hisahide ; Nishimura, Noriyuki. / Gestational age-dependent increase of survival motor neuron protein in umbilical cord-derived mesenchymal stem cells. In: Frontiers in Pediatrics. 2017 ; Vol. 5.
@article{e7a12bfb2f164f519def1b24d2ea03fb,
title = "Gestational age-dependent increase of survival motor neuron protein in umbilical cord-derived mesenchymal stem cells",
abstract = "Background: Spinal muscular atrophy (SMA) is the most common genetic neurological disease leading to infant death. It is caused by loss of survival motor neuron (SMN) 1 gene and subsequent reduction of SMN protein in motor neurons. Because SMN is ubiquitously expressed and functionally linked to general RNA metabolism pathway, fibroblasts (FBs) are most widely used for the assessment of SMN expression in SMA patients but usually isolated from skin biopsy samples after the onset of overt symptoms. Although recent translational studies of SMN-targeted therapies have revealed the very limited time window for effective SMA therapies during perinatal period, the exact time point when SMN shortage became evident is unknown in human samples. In this study, we analyzed SMN mRNA and protein expression during perinatal period by using umbilical cord-derived mesenchymal stem cells (UC-MSCs) obtained from preterm and term infants. Methods: UC-MSCs were isolated from 16 control infants delivered at 22-40 weeks of gestation and SMA fetus aborted at 19 weeks of gestation (UC-MSC-Control and UC-MSC-SMA). FBs were isolated from control volunteer and SMA patient (FB-Control and FB-SMA). SMN mRNA and protein expression in UC-MSCs and FBs was determined by RT-qPCR and Western blot. Results: UC-MSC-Control and UC-MSC-SMA expressed the comparable level of MSC markers on their cell surface and were able to differentiate into adipocytes, osteocytes, and chondrocytes. At steady state, SMN mRNA and protein expression was decreased in UC-MSC-SMA compared to UC-MSC-Control, as observed in FB-SMA and FB-Control. In response to histone deacetylase inhibitor valproic acid, SMN mRNA and protein expression in UC-MSC-SMA and FB-SMA was increased. During perinatal development from 22 to 40 weeks of gestation, SMN mRNA and protein expression in UC-MSC-Control was positively correlated with gestational age. Conclusion: UC-MSCs isolated from 17 fetus/infant of 19-40 weeks of gestation are expressed functional SMN mRNA and protein. SMN mRNA and protein expression in UC-MSCs is increased with gestational age during perinatal development.",
author = "Sota Iwatani and Harahap, {Nur Imma Fatimah} and Nurputra, {Dian Kesumapramudya} and Shinya Tairaku and Akemi Shono and Daisuke Kurokawa and Keiji Yamana and Thwin, {Khin Kyae Mon} and Makiko Yoshida and Masami Mizobuchi and Tsubasa Koda and Kazumichi Fujioka and Mariko Ikeda and Hideto Yamada and Ichiro Morioka and Kazumoto Iijima and Hisahide Nishio and Noriyuki Nishimura",
year = "2017",
month = "9",
day = "5",
doi = "10.3389/fped.2017.00194",
language = "English",
volume = "5",
journal = "Frontiers in Pediatrics",
issn = "2296-2360",
publisher = "Frontiers Media S. A.",

}

Iwatani, S, Harahap, NIF, Nurputra, DK, Tairaku, S, Shono, A, Kurokawa, D, Yamana, K, Thwin, KKM, Yoshida, M, Mizobuchi, M, Koda, T, Fujioka, K, Ikeda, M, Yamada, H, Morioka, I, Iijima, K, Nishio, H & Nishimura, N 2017, 'Gestational age-dependent increase of survival motor neuron protein in umbilical cord-derived mesenchymal stem cells', Frontiers in Pediatrics, vol. 5, 194. https://doi.org/10.3389/fped.2017.00194

Gestational age-dependent increase of survival motor neuron protein in umbilical cord-derived mesenchymal stem cells. / Iwatani, Sota; Harahap, Nur Imma Fatimah; Nurputra, Dian Kesumapramudya; Tairaku, Shinya; Shono, Akemi; Kurokawa, Daisuke; Yamana, Keiji; Thwin, Khin Kyae Mon; Yoshida, Makiko; Mizobuchi, Masami; Koda, Tsubasa; Fujioka, Kazumichi; Ikeda, Mariko; Yamada, Hideto; Morioka, Ichiro; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki.

In: Frontiers in Pediatrics, Vol. 5, 194, 05.09.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Gestational age-dependent increase of survival motor neuron protein in umbilical cord-derived mesenchymal stem cells

AU - Iwatani, Sota

AU - Harahap, Nur Imma Fatimah

AU - Nurputra, Dian Kesumapramudya

AU - Tairaku, Shinya

AU - Shono, Akemi

AU - Kurokawa, Daisuke

AU - Yamana, Keiji

AU - Thwin, Khin Kyae Mon

AU - Yoshida, Makiko

AU - Mizobuchi, Masami

AU - Koda, Tsubasa

AU - Fujioka, Kazumichi

AU - Ikeda, Mariko

AU - Yamada, Hideto

AU - Morioka, Ichiro

AU - Iijima, Kazumoto

AU - Nishio, Hisahide

AU - Nishimura, Noriyuki

PY - 2017/9/5

Y1 - 2017/9/5

N2 - Background: Spinal muscular atrophy (SMA) is the most common genetic neurological disease leading to infant death. It is caused by loss of survival motor neuron (SMN) 1 gene and subsequent reduction of SMN protein in motor neurons. Because SMN is ubiquitously expressed and functionally linked to general RNA metabolism pathway, fibroblasts (FBs) are most widely used for the assessment of SMN expression in SMA patients but usually isolated from skin biopsy samples after the onset of overt symptoms. Although recent translational studies of SMN-targeted therapies have revealed the very limited time window for effective SMA therapies during perinatal period, the exact time point when SMN shortage became evident is unknown in human samples. In this study, we analyzed SMN mRNA and protein expression during perinatal period by using umbilical cord-derived mesenchymal stem cells (UC-MSCs) obtained from preterm and term infants. Methods: UC-MSCs were isolated from 16 control infants delivered at 22-40 weeks of gestation and SMA fetus aborted at 19 weeks of gestation (UC-MSC-Control and UC-MSC-SMA). FBs were isolated from control volunteer and SMA patient (FB-Control and FB-SMA). SMN mRNA and protein expression in UC-MSCs and FBs was determined by RT-qPCR and Western blot. Results: UC-MSC-Control and UC-MSC-SMA expressed the comparable level of MSC markers on their cell surface and were able to differentiate into adipocytes, osteocytes, and chondrocytes. At steady state, SMN mRNA and protein expression was decreased in UC-MSC-SMA compared to UC-MSC-Control, as observed in FB-SMA and FB-Control. In response to histone deacetylase inhibitor valproic acid, SMN mRNA and protein expression in UC-MSC-SMA and FB-SMA was increased. During perinatal development from 22 to 40 weeks of gestation, SMN mRNA and protein expression in UC-MSC-Control was positively correlated with gestational age. Conclusion: UC-MSCs isolated from 17 fetus/infant of 19-40 weeks of gestation are expressed functional SMN mRNA and protein. SMN mRNA and protein expression in UC-MSCs is increased with gestational age during perinatal development.

AB - Background: Spinal muscular atrophy (SMA) is the most common genetic neurological disease leading to infant death. It is caused by loss of survival motor neuron (SMN) 1 gene and subsequent reduction of SMN protein in motor neurons. Because SMN is ubiquitously expressed and functionally linked to general RNA metabolism pathway, fibroblasts (FBs) are most widely used for the assessment of SMN expression in SMA patients but usually isolated from skin biopsy samples after the onset of overt symptoms. Although recent translational studies of SMN-targeted therapies have revealed the very limited time window for effective SMA therapies during perinatal period, the exact time point when SMN shortage became evident is unknown in human samples. In this study, we analyzed SMN mRNA and protein expression during perinatal period by using umbilical cord-derived mesenchymal stem cells (UC-MSCs) obtained from preterm and term infants. Methods: UC-MSCs were isolated from 16 control infants delivered at 22-40 weeks of gestation and SMA fetus aborted at 19 weeks of gestation (UC-MSC-Control and UC-MSC-SMA). FBs were isolated from control volunteer and SMA patient (FB-Control and FB-SMA). SMN mRNA and protein expression in UC-MSCs and FBs was determined by RT-qPCR and Western blot. Results: UC-MSC-Control and UC-MSC-SMA expressed the comparable level of MSC markers on their cell surface and were able to differentiate into adipocytes, osteocytes, and chondrocytes. At steady state, SMN mRNA and protein expression was decreased in UC-MSC-SMA compared to UC-MSC-Control, as observed in FB-SMA and FB-Control. In response to histone deacetylase inhibitor valproic acid, SMN mRNA and protein expression in UC-MSC-SMA and FB-SMA was increased. During perinatal development from 22 to 40 weeks of gestation, SMN mRNA and protein expression in UC-MSC-Control was positively correlated with gestational age. Conclusion: UC-MSCs isolated from 17 fetus/infant of 19-40 weeks of gestation are expressed functional SMN mRNA and protein. SMN mRNA and protein expression in UC-MSCs is increased with gestational age during perinatal development.

UR - http://www.scopus.com/inward/record.url?scp=85042038632&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042038632&partnerID=8YFLogxK

U2 - 10.3389/fped.2017.00194

DO - 10.3389/fped.2017.00194

M3 - Article

AN - SCOPUS:85042038632

VL - 5

JO - Frontiers in Pediatrics

JF - Frontiers in Pediatrics

SN - 2296-2360

M1 - 194

ER -