Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies

A continuing limitation and major challenge in the development and utilization of predictable stem cell therapies (SCTs) is the determination of the optimal dosages of stem cells. Herein, we report the quantification of stem cell fractions (SCF) of human mesenchymal stem cell (MSC) preparations deri...

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Main Authors: Hitesh Chopra, Chen Cao, Celia Sommer, Alex Dahlkemper, James Sugai, James L. Sherley, Darnell Kaigler
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/23/2703
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author Hitesh Chopra
Chen Cao
Celia Sommer
Alex Dahlkemper
James Sugai
James L. Sherley
Darnell Kaigler
author_facet Hitesh Chopra
Chen Cao
Celia Sommer
Alex Dahlkemper
James Sugai
James L. Sherley
Darnell Kaigler
author_sort Hitesh Chopra
collection DOAJ
description A continuing limitation and major challenge in the development and utilization of predictable stem cell therapies (SCTs) is the determination of the optimal dosages of stem cells. Herein, we report the quantification of stem cell fractions (SCF) of human mesenchymal stem cell (MSC) preparations derived from oral tissues. A novel computational methodology, kinetic stem cell (KSC) counting, was used to quantify the SCF and specific cell culture kinetics of stem cells in oral alveolar bone-derived MSC (aBMSCs) from eight patients. These analyses established, for the first time, that the SCF within these heterogeneous, mixed-cell populations differs significantly among donors, ranging from 7% to 77% (ANOVA <i>p</i> < 0.0001). Both the initial SCF of aBMSC preparations and changes in the level of the SCF with serial culture over time showed a high degree of inter-donor variation. Hence, it was revealed that the stability of the SCF of human aBMSC preparations during serial cell culture shows inter-donor variation, with some patient preparations exhibiting sufficient stability to support the long-term net expansion of stem cells. These findings provide important insights for the clinical-scale expansion and biomanufacturing of MSCs, which can facilitate establishing more effective and predictable outcomes in clinical trials and treatments employing SCT.
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spelling doaj.art-42d1915fe49b4757a48679ea0024a1602023-12-08T15:13:06ZengMDPI AGCells2073-44092023-11-011223270310.3390/cells12232703Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell TherapiesHitesh Chopra0Chen Cao1Celia Sommer2Alex Dahlkemper3James Sugai4James L. Sherley5Darnell Kaigler6Kaigler Lab of Stem Cell Science and Tissue Regeneration, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USAKaigler Lab of Stem Cell Science and Tissue Regeneration, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USAKaigler Lab of Stem Cell Science and Tissue Regeneration, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USAKaigler Lab of Stem Cell Science and Tissue Regeneration, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USAKaigler Lab of Stem Cell Science and Tissue Regeneration, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USAAsymmetrex®, LLC, Boston, MA 02130, USAKaigler Lab of Stem Cell Science and Tissue Regeneration, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USAA continuing limitation and major challenge in the development and utilization of predictable stem cell therapies (SCTs) is the determination of the optimal dosages of stem cells. Herein, we report the quantification of stem cell fractions (SCF) of human mesenchymal stem cell (MSC) preparations derived from oral tissues. A novel computational methodology, kinetic stem cell (KSC) counting, was used to quantify the SCF and specific cell culture kinetics of stem cells in oral alveolar bone-derived MSC (aBMSCs) from eight patients. These analyses established, for the first time, that the SCF within these heterogeneous, mixed-cell populations differs significantly among donors, ranging from 7% to 77% (ANOVA <i>p</i> < 0.0001). Both the initial SCF of aBMSC preparations and changes in the level of the SCF with serial culture over time showed a high degree of inter-donor variation. Hence, it was revealed that the stability of the SCF of human aBMSC preparations during serial cell culture shows inter-donor variation, with some patient preparations exhibiting sufficient stability to support the long-term net expansion of stem cells. These findings provide important insights for the clinical-scale expansion and biomanufacturing of MSCs, which can facilitate establishing more effective and predictable outcomes in clinical trials and treatments employing SCT.https://www.mdpi.com/2073-4409/12/23/2703mesenchymal stem cellskinetic stem cell countingalveolar bonestem cell therapycell biomanufacturing
spellingShingle Hitesh Chopra
Chen Cao
Celia Sommer
Alex Dahlkemper
James Sugai
James L. Sherley
Darnell Kaigler
Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies
Cells
mesenchymal stem cells
kinetic stem cell counting
alveolar bone
stem cell therapy
cell biomanufacturing
title Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies
title_full Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies
title_fullStr Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies
title_full_unstemmed Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies
title_short Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies
title_sort quantification of the culture stability of stem cell fractions from oral derived human mesenchymal stem cell preparations a significant step toward the clinical translation of cell therapies
topic mesenchymal stem cells
kinetic stem cell counting
alveolar bone
stem cell therapy
cell biomanufacturing
url https://www.mdpi.com/2073-4409/12/23/2703
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