Autologous, Gene-Modified Hematopoietic Stem and Progenitor Cells Repopulate the Central Nervous System with Distinct Clonal Variants

As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.

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The results of multicenter treatment of atypical teratoid/rhabdoid tumors of the central nervous system in children under 3 years

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2021-20-2-121-132 ◽

2021 ◽

Vol 20 (2) ◽

pp. 121-132

Author(s):

L. V. Olkhova ◽

O. G. Zheludkova ◽

L. S. Zubarovskaya ◽

A. Yu. Smirnova ◽

Yu. V. Dinikina ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Radiation Therapy ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

High Dose Chemotherapy ◽

High Dose ◽

Hematopoietic Stem ◽

Atypical Teratoid ◽

The Central Nervous System

Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) is an aggressive malignant tumor that is mainly found in younger children and is associated with poor prognosis. Our objectives: to present the results of treatment of children with CNS AT/RT under 3 years of age and assess the impact of various prognostic factors on patient survival. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation. The study included 106 patients with CNS AT/RT aged 0–3 years who had been treated and monitored from 2008 to 2020. The median age was 16 (9; 23) months. All the patients underwent primary tumor resection with subsequent chemotherapy according to various protocols. At the time of the analysis, 47 patients (44.4%) were alive, 1 patient (0.9%) was lost to follow-up and 58 patients (54.7%) were dead, of whom 52 patients (90%) had died of disease progression and 6 (10%) – of polychemotherapy complications. One patient developed shunt-related intraabdominal metastasis within 10 months of the diagnosis. The 1-year progression-free survival (PFS) was 0.50; the 2-year PFS was 0.29; the 5-year PFS – 0.27. The median PFS was 12 months. The 1-year overall survival (OS) was 0.72; the 2-year OS was 0.53; the 5-year OS – 0.40. The median OS was 27 months. An analysis of patients with CNS AT/RT under 3 years of age showed that PFS was statistically significantly higher in: children aged > 12 months; children with totally resected tumours; children who had received polychemotherapy in accordance with the ATRT-2006 protocol that included radiotherapy and regional administration of a triplet of chemotherapeutic agents. The OS in patients with CNS AT/RT aged < 3 years was statistically significantly higher in: children aged > 12 months; children who had been treated with radiation therapy; patients who had received cytosar/etoposide intrathecally/intraventricularly; patients who had undergone high-dose chemotherapy with subsequent autologous hematopoietic stem cell transplantation. A multivariate analysis revealed that PFS was influenced by age, tumor location, extent of resection and exposure to radiation therapy, regional chemotherapy or high-dose chemotherapy with autologous hematopoietic stem cell transplantation, while OS was affected by age and exposure to radiation therapy.

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Toxoplasmic Encephalitis Followed by Primary EBV-Associated Post-Transplant Lymphoproliferative Disorder of the Central Nervous System in a Patient Undergoing Allogeneic Hematopoietic Stem Cell Transplant: A Case Report

Transplantation Proceedings ◽

10.1016/j.transproceed.2020.08.002 ◽

2020 ◽

Vol 52 (9) ◽

pp. 2858-2860

Author(s):

Azusa Mayumi ◽

Takaya Yamashita ◽

Ikuo Matsuda ◽

Kenji Hikosaka ◽

Satoshi Fujino ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Case Report ◽

Lymphoproliferative Disorder ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Toxoplasmic Encephalitis ◽

Cell Transplant ◽

Hematopoietic Stem ◽

The Central Nervous System

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Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo

Development ◽

10.1242/dev.128.10.1757 ◽

2001 ◽

Vol 128 (10) ◽

pp. 1757-1769 ◽

Cited By ~ 3

Author(s):

C. Olivier ◽

I. Cobos ◽

E.M. Perez Villegas ◽

N. Spassky ◽

B. Zalc ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Chick Embryo ◽

Embryonic Development ◽

Progenitor Cells ◽

Oligodendrocyte Progenitor Cells ◽

Chick Brain ◽

The Central Nervous System ◽

The Brain

Oligodendrocytes are the myelin-forming cells in the central nervous system. In the brain, oligodendrocyte precursors arise in multiple restricted foci, distributed along the caudorostral axis of the ventricular neuroepithelium. In chick embryonic hind-, mid- and caudal forebrain, oligodendrocytes have a basoventral origin, while in the rostral fore-brain oligodendrocytes emerge from alar territories (Perez Villegas, E. M., Olivier, C., Spassky, N., Poncet, C., Cochard, P., Zalc, B., Thomas, J. L. and Martinez, S. (1999) Dev. Biol. 216, 98–113). To investigate the respective territories colonized by oligodendrocyte progenitor cells that originate from either the basoventral or alar foci, we have created a series of quail-chick chimeras. Homotopic chimeras demonstrate clearly that, during embryonic development, oligodendrocyte progenitors that emerge from the alar anterior entopeduncular area migrate tangentially to invade the entire telencephalon, whereas those from the basal rhombomeric foci show a restricted rostrocaudal distribution and colonize only their rhombomere of origin. Heterotopic chimeras indicate that differences in the migratory properties of oligodendroglial cells do not depend on their basoventral or alar ventricular origin. Irrespective of their origin (basal or alar), oligodendrocytes migrate only short distances in the hindbrain and long distances in the prosencephalon. Furthermore, we provide evidence that, in the developing chick brain, all telencephalic oligodendrocytes originate from the anterior entopeduncular area and that the prominent role of anterior entopeduncular area in telencephalic oligodendrogenesis is conserved between birds and mammals.

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