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Macrophage-secreted factors enhance the in vitro expansion of DMD muscle precursor cells while preserving their myogenic potential.
Neurol Res. 2010 Feb; 32(1):55-62.NR

Abstract

OBJECTIVE

Autologous cell transplantation has been proposed as a possible therapeutic approach for Duchenne dystrophy. In this approach, patients' muscle precursor cells (mpcs) obtained from muscle biopsies would be expanded ex vivo, genetically modified to restore dystrophin expression and then reimplanted in the original donor. Such strategy would have the advantage of bypassing the immune response problem, but on the other hand, it would require a large number of cells because of the poor viability and mobility of transplanted myoblasts. Besides, extensive multiplication of mpcs is difficult and can affect their myogenic ability. Given the key role of inflammation in muscle regeneration, we set out to verify if factors secreted by inflammatory cells could be used to improve in vitro expansion of DMD-mpcs.

METHODS

We have previously shown that a murine macrophage conditioned medium (mMCM) could increase the in vitro proliferation rate of rat and mouse mpcs. Here we tested the effect of mMCM on cultures of human, dystrophin-deficient mpcs (DMD-mpcs).

RESULTS

In the presence of mMCM, DMD-mpcs displayed an increased proliferation rate, while at the same time, maintaining their myogenicity after many in vitro passages. Expanded cells were also injected in muscles of immuno-deficient mice, showing that they were also able to participate in muscle regeneration within recipient muscles.

DISCUSSION

Using macrophagic factors, we were able to increase the amount of DMD-mpcs obtainable after 38 days of culture by >7 x 10(3)-fold. These findings indicate that macrophagic factors hold great potential for future use in cell transplantation protocol.

Authors+Show Affiliations

Department of Biology, University of Padova, Padova, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19108751

Citation

Malerba, Alberto, et al. "Macrophage-secreted Factors Enhance the in Vitro Expansion of DMD Muscle Precursor Cells While Preserving Their Myogenic Potential." Neurological Research, vol. 32, no. 1, 2010, pp. 55-62.
Malerba A, Pasut A, Frigo M, et al. Macrophage-secreted factors enhance the in vitro expansion of DMD muscle precursor cells while preserving their myogenic potential. Neurol Res. 2010;32(1):55-62.
Malerba, A., Pasut, A., Frigo, M., De Coppi, P., Baroni, M. D., & Vitiello, L. (2010). Macrophage-secreted factors enhance the in vitro expansion of DMD muscle precursor cells while preserving their myogenic potential. Neurological Research, 32(1), 55-62. https://doi.org/10.1179/174313209X380865
Malerba A, et al. Macrophage-secreted Factors Enhance the in Vitro Expansion of DMD Muscle Precursor Cells While Preserving Their Myogenic Potential. Neurol Res. 2010;32(1):55-62. PubMed PMID: 19108751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Macrophage-secreted factors enhance the in vitro expansion of DMD muscle precursor cells while preserving their myogenic potential. AU - Malerba,Alberto, AU - Pasut,Alessandra, AU - Frigo,Marco, AU - De Coppi,Paolo, AU - Baroni,M David, AU - Vitiello,Libero, Y1 - 2008/12/23/ PY - 2008/12/26/entrez PY - 2008/12/26/pubmed PY - 2010/3/23/medline SP - 55 EP - 62 JF - Neurological research JO - Neurol. Res. VL - 32 IS - 1 N2 - OBJECTIVE: Autologous cell transplantation has been proposed as a possible therapeutic approach for Duchenne dystrophy. In this approach, patients' muscle precursor cells (mpcs) obtained from muscle biopsies would be expanded ex vivo, genetically modified to restore dystrophin expression and then reimplanted in the original donor. Such strategy would have the advantage of bypassing the immune response problem, but on the other hand, it would require a large number of cells because of the poor viability and mobility of transplanted myoblasts. Besides, extensive multiplication of mpcs is difficult and can affect their myogenic ability. Given the key role of inflammation in muscle regeneration, we set out to verify if factors secreted by inflammatory cells could be used to improve in vitro expansion of DMD-mpcs. METHODS: We have previously shown that a murine macrophage conditioned medium (mMCM) could increase the in vitro proliferation rate of rat and mouse mpcs. Here we tested the effect of mMCM on cultures of human, dystrophin-deficient mpcs (DMD-mpcs). RESULTS: In the presence of mMCM, DMD-mpcs displayed an increased proliferation rate, while at the same time, maintaining their myogenicity after many in vitro passages. Expanded cells were also injected in muscles of immuno-deficient mice, showing that they were also able to participate in muscle regeneration within recipient muscles. DISCUSSION: Using macrophagic factors, we were able to increase the amount of DMD-mpcs obtainable after 38 days of culture by >7 x 10(3)-fold. These findings indicate that macrophagic factors hold great potential for future use in cell transplantation protocol. SN - 1743-1328 UR - https://www.unboundmedicine.com/medline/citation/19108751/Macrophage_secreted_factors_enhance_the_in_vitro_expansion_of_DMD_muscle_precursor_cells_while_preserving_their_myogenic_potential_ L2 - http://www.tandfonline.com/doi/full/10.1179/174313209X380865 DB - PRIME DP - Unbound Medicine ER -