Abstract
Owing to the beneficial properties of amniotic fluid-derived stem cells (AFSCs), including pluripotency and the lack of ethical issues associated with embryonic stem cells (ESCs), they should be a promising cell source for regenerative medicine. However, how to differentiate AFSCs into contracting cardiomyocytes has not been established. In this study, a well-established, direct cardiac differentiation protocol involving the modulation of Wnt signaling was used to differentiate Oct 3/4+ AFSCs into cardiomyocytes. By day 14 of cardiomyocyte differentiation, these AFSCs expressed cardiac-specific genes (i.e., cardiac troponin T and myosin light chain 2v) and proteins but could not spontaneously contract. Using the patch-clamp technique, we further characterized the electrophysiological properties of human ESC-derived cardiomyocytes (hESC-CMs) and differentiated AFSCs. We used different configurations to investigate membrane potentials and ion currents in differentiated AFSCs and hESC-CMs. Under cell-attached voltage- or whole-cell current-clamp modes, we recorded spontaneous action currents (ACs) or action potentials (APs) in hESC-CMs but not in differentiated AFSCs. Compared to hESC-CMs, differentiated AFSCs showed significantly diminished activity of both BKCa and IKCa channels, which might lead to a lack of spontaneous ACs and APs in differentiated AFSCs. These results indicated that this well-established Wnt signaling modulating cardiac differentiation protocol was insufficient to induce the differentiation of functional cardiomyocytes from Oct 3/4+ AFSCs. Therefore, AFSC may not be an ideal candidate for cardiomyocyte differentiation.
| Original language | English |
|---|---|
| Article number | 59 |
| Journal | Cell Death Discovery |
| Volume | 5 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2019 Dec 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Immunology
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research
Cite this
}
The biochemical and electrophysiological profiles of amniotic fluid-derived stem cells following Wnt signaling modulation cardiac differentiation. / Liu, Yen Wen; Fang, Yi Hsein; Su, Chi Ting; Hwang, Shiaw Min; Liu, Ping Yen; Wu, Sheng-Nan.
In: Cell Death Discovery, Vol. 5, No. 1, 59, 01.12.2019.Research output: Contribution to journal › Article
TY - JOUR
T1 - The biochemical and electrophysiological profiles of amniotic fluid-derived stem cells following Wnt signaling modulation cardiac differentiation
AU - Liu, Yen Wen
AU - Fang, Yi Hsein
AU - Su, Chi Ting
AU - Hwang, Shiaw Min
AU - Liu, Ping Yen
AU - Wu, Sheng-Nan
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Owing to the beneficial properties of amniotic fluid-derived stem cells (AFSCs), including pluripotency and the lack of ethical issues associated with embryonic stem cells (ESCs), they should be a promising cell source for regenerative medicine. However, how to differentiate AFSCs into contracting cardiomyocytes has not been established. In this study, a well-established, direct cardiac differentiation protocol involving the modulation of Wnt signaling was used to differentiate Oct 3/4+ AFSCs into cardiomyocytes. By day 14 of cardiomyocyte differentiation, these AFSCs expressed cardiac-specific genes (i.e., cardiac troponin T and myosin light chain 2v) and proteins but could not spontaneously contract. Using the patch-clamp technique, we further characterized the electrophysiological properties of human ESC-derived cardiomyocytes (hESC-CMs) and differentiated AFSCs. We used different configurations to investigate membrane potentials and ion currents in differentiated AFSCs and hESC-CMs. Under cell-attached voltage- or whole-cell current-clamp modes, we recorded spontaneous action currents (ACs) or action potentials (APs) in hESC-CMs but not in differentiated AFSCs. Compared to hESC-CMs, differentiated AFSCs showed significantly diminished activity of both BKCa and IKCa channels, which might lead to a lack of spontaneous ACs and APs in differentiated AFSCs. These results indicated that this well-established Wnt signaling modulating cardiac differentiation protocol was insufficient to induce the differentiation of functional cardiomyocytes from Oct 3/4+ AFSCs. Therefore, AFSC may not be an ideal candidate for cardiomyocyte differentiation.
AB - Owing to the beneficial properties of amniotic fluid-derived stem cells (AFSCs), including pluripotency and the lack of ethical issues associated with embryonic stem cells (ESCs), they should be a promising cell source for regenerative medicine. However, how to differentiate AFSCs into contracting cardiomyocytes has not been established. In this study, a well-established, direct cardiac differentiation protocol involving the modulation of Wnt signaling was used to differentiate Oct 3/4+ AFSCs into cardiomyocytes. By day 14 of cardiomyocyte differentiation, these AFSCs expressed cardiac-specific genes (i.e., cardiac troponin T and myosin light chain 2v) and proteins but could not spontaneously contract. Using the patch-clamp technique, we further characterized the electrophysiological properties of human ESC-derived cardiomyocytes (hESC-CMs) and differentiated AFSCs. We used different configurations to investigate membrane potentials and ion currents in differentiated AFSCs and hESC-CMs. Under cell-attached voltage- or whole-cell current-clamp modes, we recorded spontaneous action currents (ACs) or action potentials (APs) in hESC-CMs but not in differentiated AFSCs. Compared to hESC-CMs, differentiated AFSCs showed significantly diminished activity of both BKCa and IKCa channels, which might lead to a lack of spontaneous ACs and APs in differentiated AFSCs. These results indicated that this well-established Wnt signaling modulating cardiac differentiation protocol was insufficient to induce the differentiation of functional cardiomyocytes from Oct 3/4+ AFSCs. Therefore, AFSC may not be an ideal candidate for cardiomyocyte differentiation.
UR - http://www.scopus.com/inward/record.url?scp=85070973932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070973932&partnerID=8YFLogxK
U2 - 10.1038/s41420-019-0143-0
DO - 10.1038/s41420-019-0143-0
M3 - Article
VL - 5
JO - Cell Death Discovery
JF - Cell Death Discovery
SN - 2058-7716
IS - 1
M1 - 59
ER -