The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy

脂肪组织来源的 SVF 中的 ADSC 与 HSC 祖细胞的比例可能是预测干细胞治疗结果的关键

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作者:Mehmet Okyay Kilinc, Antonio Santidrian, Ivelina Minev, Robert Toth, Dobrin Draganov, Duong Nguyen, Elliot Lander, Mark Berman, Boris Minev, Aladar A Szalay

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.

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.

Results

Flow analysis showed that freshly isolated SVF was very heterogeneous and harbored four major subsets specific to adipose tissue; CD34high CD45- CD31- CD146- adipose-derived stromal/stem cells (ADSCs), CD34low CD45+ CD206+CD31- CD146- hematopoietic stem cell-progenitors (HSC-progenitors), CD34high 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.

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