Abstract
Recent reports have documented the differentiation of human pluripotent stem cells toward the skeletal myogenic lineage using transgene- and cell purification-free approaches. Although these protocols generate myocytes, they have not demonstrated scalability, safety, and in vivo engraftment, which are key aspects for their future clinical application. Here we recapitulate one prominent protocol, and show that it gives rise to a heterogeneous cell population containing myocytes and other cell types. Upon transplantation, the majority of human donor cells could not contribute to myofiber formation. As a proof-of-principle, we incorporated the inducible PAX7 lentiviral system into this protocol, which then enabled scalable expansion of a homogeneous population of skeletal myogenic progenitors capable of forming myofibers in vivo. Our findings demonstrate the methods for scalable expansion of PAX7+ myogenic progenitors and their purification are critical for practical application to cell replacement treatment of muscle degenerative diseases.
Citations
May 16, 2018·Stem Cells International·Nunnapas JiwlawatMasatoshi Suzuki
Sep 14, 2019·Cells·Norio MotohashiYoshitsugu Aoki
Dec 26, 2019·Disease Models & Mechanisms·Aurora FustoElena Pegoraro
Dec 13, 2019·Frontiers in Cell and Developmental Biology·Sin-Ruow TeyMasatoshi Suzuki
Jun 17, 2020·Development·Ziad Al TanouryOlivier Pourquié
Nov 13, 2018·Oxidative Medicine and Cellular Longevity·Pei-Hsun SungHon-Kan Yip
May 16, 2020·Npj Regenerative Medicine·Robert N Judson, Fabio M V Rossi
Jan 6, 2019·Cells·Jose L Ortiz-Vitali, Radbod Darabi
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Ursula KreuserSolvig Diederichs
Dec 5, 2020·Stem Cell Reports·Hyunkee KimRita C R Perlingeiro
Jul 30, 2019·Stem Cell Reports·Takahiko SatoChie Sotozono
Feb 3, 2021·Stem Cells Translational Medicine·Serena CortiRosanna Dono
May 13, 2020·Cell Stem Cell·Haibin XiApril D Pyle
Feb 14, 2021·Npj Regenerative Medicine·Robert N Judson, Fabio M V Rossi
Apr 25, 2020·Stem Cell Reports·Jennifer B KwonCharles A Gersbach
May 15, 2021·Biochemical and Biophysical Research Communications·Giulia SelminNicola Elvassore
Jul 4, 2020·Stem Cell Reports·Mingming ZhaoHidetoshi Sakurai
Jul 7, 2021·Cell Death & Disease·Natacha BreulsMaurilio Sampaolesi