TY - JOUR
T1 - A novel approach to label bone marrow-derived mesenchymal stem cells with mixed-surface PAMAM dendrimers
AU - Munro, Nikolas
AU - Srinageshwar, Bhairavi
AU - Shalabi, Firas
AU - Florendo, Maria
AU - Otero, Paulina
AU - Thompson, Cassandra
AU - Kippe, Jordyn
AU - Malkowski, Clayton
AU - Climie, Sydney
AU - Stewart, Andrew N.
AU - Kim, Rachel
AU - Zhou, Joseph
AU - Swanson, Douglas
AU - Dunbar, Gary L.
AU - Sharma, Ajit
AU - Rossignol, Julien
N1 - Funding Information:
This research was supported by the Field Neurosciences Institute, the John G. Kulhavi Professorship, Department of Chemistry and Biochemistry, The CMU Program in Neuroscience and the CMU College of Medicine. The authors had no conflicts of interest and gratefully acknowledges the support of these sponsors.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/2/28
Y1 - 2019/2/28
N2 - Background: Transplantation of mesenchymal stem cells has created enormous opportunities as a potential treatment for various diseases including neurodegenerative diseases. Given current techniques, such as Hoechst labeling, have safety and leakage issues, our study focused, as a proof-of-concept, on a new dendrimer-based technique for labeling these stem cells to ensure their efficacy and safety following transplantation into the brain of a healthy mice. Methods and results: The bone marrow-derived mesenchymal stem cells (BM-MSCs) were labeled using polyaminoamine (PAMAM) dendrimers following which their stemness based on their proliferation and differentiation ability were analyzed by gold standard methods. These labeled BM-MSCs were transplanted into the striatum of C57BL/6J mice and were tracked using in vivo imaging system (IVIS) and analyzed using tissue imaging, 2 weeks after transplantation. Our results showed that the dendrimer-labeled BM-MSCs were able to successfully maintain their stemness and were tracked in vivo following transplantation. Unlike Hoechst, we did not find the dendrimers to be leaking out of the cells and were very specific to the cells that up took the dendrimers. Moreover, no adverse events were found in the transplanted animals proving that this is a safer method. Conclusions: Labeling BM-MSCs using fluorescently tagged PAMAM dendrimers can be used as a potentially safe and efficient method for labeling cells, particularly stem cells, in vitro and in vivo following transplantation in rodents.
AB - Background: Transplantation of mesenchymal stem cells has created enormous opportunities as a potential treatment for various diseases including neurodegenerative diseases. Given current techniques, such as Hoechst labeling, have safety and leakage issues, our study focused, as a proof-of-concept, on a new dendrimer-based technique for labeling these stem cells to ensure their efficacy and safety following transplantation into the brain of a healthy mice. Methods and results: The bone marrow-derived mesenchymal stem cells (BM-MSCs) were labeled using polyaminoamine (PAMAM) dendrimers following which their stemness based on their proliferation and differentiation ability were analyzed by gold standard methods. These labeled BM-MSCs were transplanted into the striatum of C57BL/6J mice and were tracked using in vivo imaging system (IVIS) and analyzed using tissue imaging, 2 weeks after transplantation. Our results showed that the dendrimer-labeled BM-MSCs were able to successfully maintain their stemness and were tracked in vivo following transplantation. Unlike Hoechst, we did not find the dendrimers to be leaking out of the cells and were very specific to the cells that up took the dendrimers. Moreover, no adverse events were found in the transplanted animals proving that this is a safer method. Conclusions: Labeling BM-MSCs using fluorescently tagged PAMAM dendrimers can be used as a potentially safe and efficient method for labeling cells, particularly stem cells, in vitro and in vivo following transplantation in rodents.
KW - Cell labeling technique
KW - Cell transplantation
KW - Hoechst
KW - Imaging
KW - Mesenchymal stem cells
KW - PAMAM dendrimer nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=85062455712&partnerID=8YFLogxK
U2 - 10.1186/s13287-019-1171-7
DO - 10.1186/s13287-019-1171-7
M3 - Article
C2 - 30819246
AN - SCOPUS:85062455712
SN - 1757-6512
VL - 10
JO - Stem Cell Research and Therapy
JF - Stem Cell Research and Therapy
IS - 1
M1 - 71
ER -