Adult bone marrow neural crest stem cells and mesenchymal stem cells are not able to replace lost neurons in acute MPTP-lesioned mice
Authors: Alice Marquet
Virginie Neirinckx
Bernard Rogister
Cécile Coste
Sabine Wislet-Gendebien
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Adult bone marrow stroma; multipotent stem cells; mesenchymal; neural-crest derived; in vitro differentiation
Affiliations: Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), Unit of Neurosciences, University of Liege, Liège, Belgium.

Abstract:  Adult bone marrow stroma contains multipotent stem cells (BMSC) that are a mixed population of mesenchymal and neural-crest derived stem cells. Both cells are endowed with in vitro multi-lineage differentiation abilities, then constituting an attractive and easy-available source of material for cell therapy in neurological disorders. Whereas the in vivo integration and differentiation of BMSC in neurons into the central nervous system is currently matter of debate, we report here that once injected into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, pure populations of either bone marrow neural crest stem cells (NCSC) or mesenchymal stem cells (MSC) survived only transiently into the lesioned brain. Moreover, they do not migrate through the brain tissue, neither modify their initial phenotype, while no recovery of the dopaminergic system integrity was observed. Consequently, we tend to conclude that MSC/NCSC are not able to replace lost neurons in acute MPTP-lesioned dopaminergic system through a suitable integration and/or differentiation process. Altogether with recent data, it appears that neuroprotective, neurotrophic and anti-inflammatory features characterizing BMSC are of greater interest as regards CNS lesions management. 

Retracted: No

PubPeer comments:
 Concerns about Figures 2 and 5. * Marked in blue: Two midbrain panels representing different time points appear to look similar, i.e. Figure 2A Control (14 days post MPTP) and Figure 5A Control (PBS PBS) (28 days post MPTP) * Marked in lime green: Two striatum panels representing different time points and different mice appear to look similar, i.e. Figure 2A MPTP (14 days post MPTP) and Figure 5A MPTP-NCSCmix (70 days post MPTP) * Marked in red: Two midbrain panels representing different mice appear to look similar, i.e. Figure 5A MPTP-PBS mice and Figure 5A MPTP mice -MSCmix graft. The photos are not direct duplicates, because they differ in the presence of a  hole and the darkness of the staining in the highly relevant Substancia Nigra pars compacta region. These 2 different features are highlighted with thin red ellipses. Could the authors please explain what happened here? ![file] ![file] , 
 Figure S1b (supplemental). * In orange: The MPTP mice 14 days panel appears to contain a region that is highly similar to a region in the Control mice 70 days. Of note, other areas in the photos are very different. * The MPTP mice 14 days panel has an unexpected square, around a green pixel in the bottom left. Could the authors please explain what happened here? ![file] , 
 Panels in Figure 1 of this paper look similar to panels in other papers. This paper is part of a set of 5 papers that all appear to contain similar panels. Similar looking panels are shown in red (SOX10), yellow (Nestin) and aqua (p75NTR). The panels might represent the same experiments, but it is strange that they are reused over a period of 6 years. * A. Glejzer et al., Cell. Mol. Life Sci. (2011) 68:2101u20132114. DOI 10.1007 s00018-010-0558-5 * Wislet-Gendebien et al., PLoS ONE 7(10): e46425 (2012). doi:10.1371 journal.pone.0046425 * Neirinckx et al., PLoS ONE 8(5): e64723 (2013). doi: 10.1371 journal.pone.0064723 (this paper) * Wislet-Gendebien et al., Cellular and Molecular Life Sciences, 69(15):2593-2608 (2012). doi: 10.1007 s00018-012-0937-1 * Coste et al., PLoS ONE 12(7): e0177962 (2017). DOI: 10.1371 journal.pone.0177962 ![file] ![file] ![file] , 
 28 October 2021 Expression of Concern. https: journals.plos.org plosone article?id=10.1371 journal.pone.0256488 Following the publication of this article [1] concerns were raised regarding results presented in Figs 1, 2 and 5, and S1 Fig. Specifically, The SOX10 panel in Fig 1D appears similar to the SOX10 results in Figure 1E of [2], the SOX10 results in Figure 2C of [4], and the SOX10 results in Fig 1F of [5]. The Nestin panel in Fig 1E appears similar to the Nestin results in Figure 1C of [2], and the Nestin results in Figure 2D of [3 retracted in 6]. Within this article [1] the following panels appear more similar than would be expected from independent samples: Figure 2A Control Midbrain (14 days post-MPTP injection) and Fig 5A Control (PBS-PBS) NSpc (28 days post-MPTP injection). Figure 2A MPTP Striatum (14 days post-MPTP injection) and Fig 5B 70 days Striatum. Fig 5A MPTP-PBS SNpc and Fig 5C 28 days SNpc. S1B Fig MPTP Mice 14 days and S1B Fig Control Mice 70 days. The authors explained that this study follows up from the results previously described in their Cellular and Molecular Life Sciences and PLOS ONE articles [2, 3 retracted in 6, 4], and preludes their PLOS ONE article [5], and clarify that the SOX10 panel in Fig 1D and the Nestin panel in Fig 1E represent the same experimental conditions as those panels presented in their other publications. As the original Figures presented in Fig 1D and 1E are not licensed for reproduction and distribution under the terms of the Creative Commons Attribution License (or Public Domain License for US gov), this article was republished on October 28, 2021 to remove this content and replace it with alternative relevant immunological characterization images. Please download this article again to view the correct version. Furthermore, the authors explain that the wrong images were used to prepare the Fig 5A MPTP effect SNpc and MTPT + NCSC Stratum 70 days panels, the Fig 5C SNpc panel and the S1B Fig 70 days panel. The authors clarify that the wrong images were used inadvertently during figure preparation and explain that this error was introduced during the preparation of the figure; the correct samples were used for the quantification and the preparation of the associated graphs. The updated figures below were provided to relay the correct panels for Fig 5, but the authors explained that they were unable to provide a replacement panel for the S1B Fig 70 days result and S1 Fig has been updated to remove the incorrect panel. The originally published, uncorrected version of S1 Fig is provided in the S6 File below. The updated Figs 1 and 5, and S1 Fig and their respective figure captions are provided here. The Board of Ethics and Scientific Integrity of the University of Liu00e8ge investigated the overlap between the aforementioned panels and recommended the article be corrected. In addition, a member of PLOS ONEu2019s Editorial Board advised that the updated figures support the results and conclusions reported in the original article. However, the PLOS ONE Editors issue this Expression of Concern to due to the number of panels affected and the unavailability of the original MSCmix transplanted brains Control Mice 70 days results. References 1.Neirinckx V, Marquet A, Coste C, Rogister B, Wislet-Gendebien S (2013) Adult Bone Marrow Neural Crest Stem Cells and Mesenchymal Stem Cells Are Not Able to Replace Lost Neurons in Acute MPTP-Lesioned Mice. PLoS ONE 8(5): e64723. pmid:23741377 2.Wislet-Gendebien S, Poulet C, Neirinckx V, Hennuy B, Swingland JT, Laudet E, et al. (2012) In Vivo Tumorigenesis Was Observed after Injection of In Vitro Expanded Neural Crest Stem Cells Isolated from Adult Bone Marrow. PLoS ONE 7(10): e46425. pmid:23071568 3.Wislet-Gendebien S., Laudet E., Neirinckx V. et al. (2012) RETRACTED ARTICLE: Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences. Cell. Mol. Life Sci. 69, 2593u20132608. pmid:22349262 4.Glejzer A., Laudet E., Leprince P. et al. (2011) Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow. Cell. Mol. Life Sci. 68, 2101u20132114. pmid:20976520 5.Coste C, Neirinckx V, Sharma A, Agirman G, Rogister B, Foguenne J, et al. (2017) Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues. PLoS ONE 12(7): e0177962. pmid:28683107 6.Wislet-Gendebien S, Laudet E, Neirinckx V. et al. (2021) Retraction Note: Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences. Cell. Mol. Life Sci. 78, 5041. pmid:33963879 ,