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The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy
BACKGROUND: Stromal vascular fraction (SVF) represents an attractive source of adult stem cells and progenitors, holding great promise for numerous cell therapy approaches. In 2017, it was reported that 1524 patients received autologous SVF following the enzymatic digestion of liposuction fat. The t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803165/ https://www.ncbi.nlm.nih.gov/pubmed/29417261 http://dx.doi.org/10.1186/s40169-018-0183-8 |
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author | Kilinc, Mehmet Okyay Santidrian, Antonio Minev, Ivelina Toth, Robert Draganov, Dobrin Nguyen, Duong Lander, Elliot Berman, Mark Minev, Boris Szalay, Aladar A. |
author_facet | Kilinc, Mehmet Okyay Santidrian, Antonio Minev, Ivelina Toth, Robert Draganov, Dobrin Nguyen, Duong Lander, Elliot Berman, Mark Minev, Boris Szalay, Aladar A. |
author_sort | Kilinc, Mehmet Okyay |
collection | PubMed |
description | BACKGROUND: Stromal vascular fraction (SVF) represents an attractive source of adult stem cells and progenitors, holding great promise for numerous cell therapy approaches. In 2017, it was reported that 1524 patients received autologous SVF following the enzymatic digestion of liposuction fat. The treatment was safe and effective and patients showed significant clinical improvement. In a collaborative study, we analyzed SVF obtained from 58 patients having degenerative, inflammatory, autoimmune diseases, and advanced stage cancer. RESULTS: Flow analysis showed that freshly isolated SVF was very heterogeneous and harbored four major subsets specific to adipose tissue; CD34(high) CD45(−) CD31(−) CD146(−) adipose-derived stromal/stem cells (ADSCs), CD34(low) CD45(+) CD206(+)CD31(−) CD146(−) hematopoietic stem cell-progenitors (HSC-progenitors), CD34(high) CD45(−) CD31(+)CD146(+) adipose tissue-endothelial cells and CD45(−)CD34(−)CD31(−)CD146(+) pericytes. Culturing and expanding of SVF revealed a homogenous population lacking hematopoietic lineage markers CD45 and CD34, but were positive for CD90, CD73, CD105, and CD44. Flow cytometry sorting of viable individual subpopulations revealed that ADSCs had the capacity to grow in adherent culture. The identity of the expanded cells as mesenchymal stem cells (MSCs) was further confirmed based on their differentiation into adipogenic and osteogenic lineages. To identify the potential factors, which may determine the beneficial outcome of treatment, we followed 44 patients post-SVF treatment. The gender, age, clinical condition, certain SVF-dose and route of injection, did not play a role on the clinical outcome. Interestingly, SVF yield seemed to be affected by patient’s characteristic to various extents. Furthermore, the therapy with adipose-derived and expanded-mesenchymal stem cells (ADE-MSCs) on a limited number of patients, did not suggest increased efficacies compared to SVF treatment. Therefore, we tested the hypothesis that a certain combination, rather than individual subset of cells may play a role in determining the treatment efficacy and found that the combination of ADSCs to HSC-progenitor cells can be correlated with overall treatment efficacy. CONCLUSIONS: We found that a 2:1 ratio of ADSCs to HSC-progenitors seems to be the key for a successful cell therapy. These findings open the way to future rational design of new treatment regimens for individuals by adjusting the cell ratio before the treatment. |
format | Online Article Text |
id | pubmed-5803165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-58031652018-02-14 The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy Kilinc, Mehmet Okyay Santidrian, Antonio Minev, Ivelina Toth, Robert Draganov, Dobrin Nguyen, Duong Lander, Elliot Berman, Mark Minev, Boris Szalay, Aladar A. Clin Transl Med Research BACKGROUND: Stromal vascular fraction (SVF) represents an attractive source of adult stem cells and progenitors, holding great promise for numerous cell therapy approaches. In 2017, it was reported that 1524 patients received autologous SVF following the enzymatic digestion of liposuction fat. The treatment was safe and effective and patients showed significant clinical improvement. In a collaborative study, we analyzed SVF obtained from 58 patients having degenerative, inflammatory, autoimmune diseases, and advanced stage cancer. RESULTS: Flow analysis showed that freshly isolated SVF was very heterogeneous and harbored four major subsets specific to adipose tissue; CD34(high) CD45(−) CD31(−) CD146(−) adipose-derived stromal/stem cells (ADSCs), CD34(low) CD45(+) CD206(+)CD31(−) CD146(−) hematopoietic stem cell-progenitors (HSC-progenitors), CD34(high) CD45(−) CD31(+)CD146(+) adipose tissue-endothelial cells and CD45(−)CD34(−)CD31(−)CD146(+) pericytes. Culturing and expanding of SVF revealed a homogenous population lacking hematopoietic lineage markers CD45 and CD34, but were positive for CD90, CD73, CD105, and CD44. Flow cytometry sorting of viable individual subpopulations revealed that ADSCs had the capacity to grow in adherent culture. The identity of the expanded cells as mesenchymal stem cells (MSCs) was further confirmed based on their differentiation into adipogenic and osteogenic lineages. To identify the potential factors, which may determine the beneficial outcome of treatment, we followed 44 patients post-SVF treatment. The gender, age, clinical condition, certain SVF-dose and route of injection, did not play a role on the clinical outcome. Interestingly, SVF yield seemed to be affected by patient’s characteristic to various extents. Furthermore, the therapy with adipose-derived and expanded-mesenchymal stem cells (ADE-MSCs) on a limited number of patients, did not suggest increased efficacies compared to SVF treatment. Therefore, we tested the hypothesis that a certain combination, rather than individual subset of cells may play a role in determining the treatment efficacy and found that the combination of ADSCs to HSC-progenitor cells can be correlated with overall treatment efficacy. CONCLUSIONS: We found that a 2:1 ratio of ADSCs to HSC-progenitors seems to be the key for a successful cell therapy. These findings open the way to future rational design of new treatment regimens for individuals by adjusting the cell ratio before the treatment. Springer Berlin Heidelberg 2018-02-07 /pmc/articles/PMC5803165/ /pubmed/29417261 http://dx.doi.org/10.1186/s40169-018-0183-8 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Kilinc, Mehmet Okyay Santidrian, Antonio Minev, Ivelina Toth, Robert Draganov, Dobrin Nguyen, Duong Lander, Elliot Berman, Mark Minev, Boris Szalay, Aladar A. The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy |
title | The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy |
title_full | The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy |
title_fullStr | The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy |
title_full_unstemmed | The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy |
title_short | The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy |
title_sort | ratio of adscs to hsc-progenitors in adipose tissue derived svf may provide the key to predict the outcome of stem-cell therapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803165/ https://www.ncbi.nlm.nih.gov/pubmed/29417261 http://dx.doi.org/10.1186/s40169-018-0183-8 |
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