Placental mesenchymal stem cells

May 31, 2017 | Autor: Nicholas Fisk | Categoria: Humans, Placenta, Mesenchymal Stem Cell, Embryonic Stem Cells, Mesenchymal Stromal Cells
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Letters to the Editors

www. AJOG.org

Placental mesenchymal stem cells TO THE EDITORS: Despite your editorialist’s caution, Portmann-Lanz et al’s recent report that the first trimester placenta contains mesenchymal stem cells (MSC) holds considerable relevance for the development of prenatal cell therapy.1 We and others have previously shown that the first-trimester fetus is a rich source of mesenchymal stem cells (MSC), which have greater expansion and differentiation ability than adult MSC, and can be readily transduced without impairing their stem cell properties.2-4 Rather than harvest fetal blood or liver MSC for autologous ex vivo gene therapy via endoscopic or ultrasoundguided fetal sampling, Portmann-Lanz’s report suggests that MSC might be more safely and simply obtained by chorion villus sampling. Although promising, however, their claim that their otherwise standard MSC from the placenta have extralineage myogenic and neurogenic potential needs to be viewed with some caution. The authors state that myogenic differentiation in the presence of a cocktail of horse serum and steroids resulted in the development of myotubes, expression of MyoD1, and myosin heavy chain (MyHC) in up to 60% of the culture. However, no evidence of myotube formation is demonstrated in their figures, which instead show immunostaining for MyoD1 in almost 100% of the cells rather than 15% to 60% described, with cytoplasmic staining of what should be a nuclear antigen. Similarly, the example of MyHC expression shown suggests nuclear staining rather than the expected cytoplasmic staining, with the magnification too low to delineate the intracytoplasmic striations associated with true myofibrils. The lack of nuclear counterstaining and the absence of both undifferentiated and positive controls indicate further methodologic weakness. We recently reported that fetal MSC from first-trimester blood and bone marrow undergo robust mature myotube formation and contribute to muscle regeneration in vivo when exposed to galectin-1, but not with a cocktail similar to that used by Portmann-Lanz et al.2 Similarly, in documenting placental MSC’s neurogenic potential, the quality of immunostaining in the figures could have been improved, to avoid the high background staining evident in almost all cells rather than the 20% to 30% reported. There was no NF200 or nestin immunostaining resembling intracellular filaments associated with these proteins. It would have been preferable to employ double/triple labeling to substantiate the presence of the 3 differentiated subpopulations claimed. Again, the data would be stronger if undifferentiated and other controls were included.

As hereditary muscle and central nervous system disorders will be mainstream targets for prenatal stem cell transplantation, it is important these methodologic issues be clarif fied. Jerry Chan, MBBCh, MRCOG Institute of Reproductive and Developmental Biology Imperial College London London, United Kingdom Centre for Fetal Care Queen Charlotte’s and Chelsea Hospital London, United Kingdom Department of Obstetrics and Gynaecology London, United Kingdom Yong Loo Lin School of Medicine National University of Singapore, Singapore Contact Dr Chan at [email protected] Nigel L. Kennea, MBBChir, MRCPCH Institute of Reproductive and Developmental Biology Imperial College London London, United Kingdom Department of Neonatology St Georges Hospital London, United Kingdom Nicholas M. Fisk, PhD, FRCOG Institute of Reproductive and Developmental Biology Imperial College London London, United Kingdom Centre for Fetal Care Queen Charlotte’s and Chelsea Hospital London, United Kingdom REFERENCES 1. Portmann-Lanz CB, Schoeberlein A, Huber A, Sager R, Malek A, Holzgreve W, et al. Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am J Obstet Gynecol 2006;194:664-73. 2. Chan J, O’Donoghue K, Gavina M, Torrente Y, Kennea N, Mehmet H, et al. Galectin-1 induces skeletal muscle differentiation in human fetal mesenchymal stem cells and increases muscle regeneration in vivo. Stem Cells 2006;24:1879-91. 3. Chan J, O’Donoghue K, de la Fuente J, Roberts IA, Kumar S, Morgan JE, et al. Human fetal mesenchymal stem cells as vehicles for gene delivery. Stem Cells 2005;23:93-102. 4. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/progenitor cells in human firsttrimester fetal blood, liver, and bone marrow. Blood 2001;98:2396-402. © 2007 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2006.08.002

REPLY We thank Chan et al1 for their interesting comments on our report about placental mesenchymal stem cells from the human placenta. We see the novelty of our results on the one hand in opening up of new sources of mesenchymal stem cells (MSCs) in placenta e18

American Journal of Obstetrics & Gynecology FEBRUARY 2007

and fetal membranes, and on the other hand in demonstrating an extra-lineage differentiation potential of these cells. Whereas previous studies were concentrating on MSCs from fetal liver, fetal blood, or from term placenta, we isolated and

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