title: MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs.
abstract: Mesenchymal stem or stromal cells (MSCs) have many potential therapeutic applications including therapies for cancers and tissue damages caused by cancers or radical cancer treatments. However, tissue-derived MSCs such as bone marrow MSCs (BM-MSCs) may promote cancer progression and have considerable donor variations and limited expandability. These issues hinder the potential applications of MSCs, especially those in cancer patients. To circumvent these issues, we derived MSCs from transgene-free human induced pluripotent stem cells (iPSCs) efficiently with a modified protocol that eliminated the need of flow cytometric sorting. Our iPSC-derived MSCs were readily expandable, but still underwent senescence after prolonged culture and did not form teratomas. These iPSC-derived MSCs homed to cancers with efficiencies similar to BM-MSCs but were much less prone than BM-MSCs to promote the epithelial-mesenchymal transition, invasion, stemness, and growth of cancer cells. The observations were probably explained by the much lower expression of receptors for interleukin-1 and TGFβ, downstream protumor factors, and hyaluronan and its cofactor TSG6, which all contribute to the protumor effects of BM-MSCs. The data suggest that iPSC-derived MSCs prepared with the modified protocol are a safer and better alternative to BM-MSCs for therapeutic applications in cancer patients. The protocol is scalable and can be used to prepare the large number of cells required for "off-the-shelf" therapies and bioengineering applications.
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Gregory
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Ryang Hwa
authors.initials: RH
authors.lastname: Lee
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Roxanne L
authors.initials: RL
authors.lastname: Reger
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Lizheng
authors.initials: L
authors.lastname: Qin
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Bo
authors.initials: B
authors.lastname: Hai
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Park
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Nara
authors.initials: N
authors.lastname: Yoon
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Bret
authors.initials: B
authors.lastname: Clough
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.
authors.forename: Eoin
authors.initials: E
authors.lastname: McNeill
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502 prockop@medicine.tamhsc.edu fliu@medicine.tamhsc.edu.
authors.forename: Darwin J
authors.initials: DJ
authors.lastname: Prockop
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502 prockop@medicine.tamhsc.edu fliu@medicine.tamhsc.edu.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D064593:Heterografts; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness
keywords: cancer; iPS cells; mesenchymal stem cells; protumor effects; tumor tropism