title: Tropism of the in situ growth from biopsies of childhood neuroectodermal tumors following transplantation into experimental teratoma.
abstract: Experimental teratoma induced from human pluripotent stem cells with normal karyotype can be described as a failed embryonic process and includes besides advanced organoid development also large elements of tissue with a prolonged occurrence of immature neural components. Such immature components, although benign, exhibit strong morphological resemblance with tumors of embryonic neuroectodermal origin. Here, we demonstrate that biopsy material from childhood tumors of neural embryonic origin transplanted to mature experimental teratoma can show an exclusive preference for matching tissue. Tumor specimens from five children with; Supratentorial primitive neuroectodermal tumor (sPNET); Pilocytic astrocytoma of the brainstem; Classic medulloblastoma; peripheral primitive neuroectodermal tumor (pPNET) or neuroblastoma (NB), respectively, were transplanted. Analysis of up to 120 sections of each tumor revealed an engraftment for three of the transplanted tumors: pPNET, sPNET, and NB, with a protruding growth from the latter two that were selected for detailed examination. The histology revealed a strict tropism with a non-random integration into what morphologically appeared as matched embryonic microenvironment recuperating the patient tumor histology. The findings suggest specific advantages over xenotransplantation and lead us to propose that transplantation to the human embryonic microenvironment in experimental teratoma can be a well-needed complement for preclinical in vivo studies of childhood neuroectodermal tumors.
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Seema
authors.initials: S
authors.lastname: Jamil
authors.forename: Isabell
authors.initials: I
authors.lastname: Hultman
authors.forename: Jessica
authors.initials: J
authors.lastname: Cedervall
authors.forename: Rouknuddin Q
authors.initials: RQ
authors.lastname: Ali
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fuchs
authors.forename: Bengt
authors.initials: B
authors.lastname: Gustavsson
authors.forename: Jurate
authors.initials: J
authors.lastname: Asmundsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Sandstedt
authors.forename: Per
authors.initials: P
authors.lastname: Kogner
authors.forename: Lars
authors.initials: L
authors.lastname: Ährlund-Richter
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000473:pathology; D001706:Biopsy / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000473:pathology; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology; D018242:Neuroectodermal Tumors, Primitive / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000473:pathology; D013724:Teratoma / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000379:methods; D018523:Tropism / Q000502:physiology*
keywords: biopsy; childhood; human; in vivo; model; neuroectodermal tumor; stem cells