Faculty Opinions recommendation of Expansion and preservation of the functional activity of adult hematopoietic stem cells cultured ex vivo with a histone deacetylase inhibitor.

Abstract Back ground Adipose tissue derived mesenchymal stem cells (ASCs) have unique potential for regenerative cell therapies. However, during ex-vivo cultivation, they undergo considerable quality loss regarding their phenotypic properties, stemness genes expression and differentiation potential. Recent studies reported that the loss of stemness properties of MSCs is a result of chromatin histone deacetylations through in-vitro cultivation. The present work aimed to study the effect of Trapoxin A (TPX) as a histone deacetylase inhibitor (HDACi) on overall stemness properties of ASCs. Methods First, the effects of TPX treatments on ASCs viability and proliferation were evaluated using MTT assay. Second, the desired doses of TPX supporting ASCs proliferation were determined and the lack of their negative effects was confirmed by DAPI staining. In addition, the influence of TPX on cell cycle of ASCs and the mRNA levels of stemness genes were measured by flowcytometry and qPCR, respectively. Finally, the effect of TPX treatment on osteogenic potential of ASCs was studied. Results The results indicated that short time TPX treatment (nM concentrations) caused stimulation of proliferation and considerable percentage of ASCs entered to S-phase of cell cycle (p<0.05). Moreover, the findings demonstrated significant up-regulation of stemness markers genes (Oct-4, Sox-2, Nanog, TERT, Klf-4, Rex-1) (p<0.05) and enhanced osteogenic differentiation potential of ASC after TPX treatment. Conclusion The addition of low dose of TPX to the expansion medium could possibly enhance the stemness properties and prevent the quality decline of ex-vivo cultured ASCs.

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Histone deacetylase inhibitor treatment downregulates VLA-4 adhesion in hematopoietic stem cells and acute myeloid leukemia blast cells

Haematologica ◽

10.3324/haematol.11796 ◽

2008 ◽

Vol 93 (3) ◽

pp. 443-446 ◽

Cited By ~ 25

Author(s):

U. Mahlknecht ◽

C. Schonbein

Keyword(s):

Stem Cells ◽

Acute Myeloid Leukemia ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Myeloid Leukemia ◽

Hematopoietic Stem ◽

Deacetylase Inhibitor ◽

Blast Cells ◽

Inhibitor Treatment ◽

Acute Myeloid

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Histone deacetylase inhibitors induce leukemia gene expression in cord blood hematopoietic stem cells expanded ex vivo

International Journal of Hematology ◽

10.1007/s12185-016-2075-2 ◽

2016 ◽

Vol 105 (1) ◽

pp. 37-43 ◽

Cited By ~ 5

Author(s):

Yuk Man Lam ◽

Yuen Fan Chan ◽

Li Chong Chan ◽

Ray Kit Ng

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Hematopoietic Stem Cells ◽

Cord Blood ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitors ◽

Ex Vivo ◽

Hematopoietic Stem

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Faculty Opinions recommendation of Ex vivo expansion of human hematopoietic stem cells by direct delivery of the HOXB4 homeoprotein.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1016469.201396 ◽

2003 ◽

Author(s):

Miles Wilkinson

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Ex Vivo ◽

Ex Vivo Expansion ◽

Hematopoietic Stem ◽

Direct Delivery

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Strategies to Protect Hematopoietic Stem Cells from Culture-Induced Stress Conditions

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200225091339 ◽

2020 ◽

Vol 15 ◽

Author(s):

Fatima Aerts-Kaya

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Ex Vivo ◽

Stress Conditions ◽

Stress Factors ◽

Hematopoietic Stem ◽

Induced Stress

: In contrast to their almost unlimited potential for expansion in vivo and despite years of dedicated research and optimization of expansion protocols, the expansion of Hematopoietic Stem Cells (HSCs) in vitro remains remarkably limited. Increased understanding of the mechanisms that are involved in maintenance, expansion and differentiation of HSCs will enable the development of better protocols for expansion of HSCs. This will allow procurement of HSCs with long-term engraftment potential and a better understanding of the effects of the external influences in and on the hematopoietic niche that may affect HSC function. During collection and culture of HSCs, the cells are exposed to suboptimal conditions that may induce different levels of stress and ultimately affect their self-renewal, differentiation and long-term engraftment potential. Some of these stress factors include normoxia, oxidative stress, extra-physiologic oxygen shock/stress (EPHOSS), endoplasmic reticulum (ER) stress, replicative stress, and stress related to DNA damage. Coping with these stress factors may help reduce the negative effects of cell culture on HSC potential, provide a better understanding of the true impact of certain treatments in the absence of confounding stress factors. This may facilitate the development of better ex vivo expansion protocols of HSCs with long-term engraftment potential without induction of stem cell exhaustion by cellular senescence or loss of cell viability. This review summarizes some of available strategies that may be used to protect HSCs from culture-induced stress conditions.

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A Review of Evaluating Hematopoietic Stem Cells Derived from Umbilical Cord Blood's Expansion and Homing

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200124115444 ◽

2020 ◽

Vol 15 (3) ◽

pp. 250-262

Author(s):

Maryam Islami ◽

Fatemeh Soleimanifar

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Umbilical Cord ◽

Stromal Cells ◽

Ex Vivo ◽

Hematologic Malignancies ◽

Future Directions ◽

Hematopoietic Stem ◽

Efficient Procedure ◽

Hematopoietic Recovery

Transplantation of hematopoietic stem cells (HSCs) derived from umbilical cord blood (UCB) has been taken into account as a therapeutic approach in patients with hematologic malignancies. Unfortunately, there are limitations concerning HSC transplantation (HSCT), including (a) low contents of UCB-HSCs in a single unit of UCB and (b) defects in UCB-HSC homing to their niche. Therefore, delays are observed in hematopoietic and immunologic recovery and homing. Among numerous strategies proposed, ex vivo expansion of UCB-HSCs to enhance UCB-HSC dose without any differentiation into mature cells is known as an efficient procedure that is able to alter clinical treatments through adjusting transplantation-related results and making them available. Accordingly, culture type, cytokine combinations, O2 level, co-culture with mesenchymal stromal cells (MSCs), as well as gene manipulation of UCB-HSCs can have effects on their expansion and growth. Besides, defects in homing can be resolved by exposing UCB-HSCs to compounds aimed at improving homing. Fucosylation of HSCs before expansion, CXCR4-SDF-1 axis partnership and homing gene involvement are among strategies that all depend on efficiency, reasonable costs, and confirmation of clinical trials. In general, the present study reviewed factors improving the expansion and homing of UCB-HSCs aimed at advancing hematopoietic recovery and expansion in clinical applications and future directions.

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