Effects of UM171 and SR1 on ex vivo expansion of hematopoietic stem and progenitor cells from different sources

doi:10.3877/cma.j.issn.2095-1221.2020.02.003

Abstract

Abstract:

Objective

To investigate the effects of small molecule compounds UM171 and SR1 on hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood (CB) , donor mobilized peripheral blood (Donor-mPB) and autologous mobilized peripheral blood (Auto-mPB) .

Methods

HSPCs from three sources were cultured with or without UM171 and SR1, and named control group, UM171 group, SR1 group and UM171+SR1 group.The number of total nucleated cells in each group was detected by cell counting. The proportion and differentiation of HSPCs and the expression of CXCR4 on HSPCs were detected by flow cytometry.One-way ANOVA and Kruskal- Wallis test were used for statistical analysis.

Results

Compared with control group, the proportions of HSPCs from three sources were increased both after treatment of UM171 and SR1. And the treatment of UM171 could increase the expansion folds of HSPCs from three sources significantly. Compared with control group, UM171 treatment led an increase in the proportion of CD33⁺ (myeloid) cells as well as a decrease in the proportion of CD41⁺ (megakaryocyte) cells from CB-derived HSPCs, SR1 treatment led an increase in the proportion of CD3^- CD56⁺ (natural killer) cells from HSPCs from three sources. The expression of CXCR4 on HSPCs in each group increased significantly after 48 h of ex vivo expansion relative to that before culture.

Conclusion

UM171 could effectively expand the number of HSPCs from CB, Donor-mPB, Auto-mPB and promote the differentiation of CB-derived HSPCs into myeloid cells as well as inhibit their differentiation into megakaryocytes. SR1 could promote the differentiation of HSPCs from three sources into natural killer cells. The expression of CXCR4 on HSPCs from three sources was increased significantly after ex vivo expansion.

Key words: Small molecule compounds, Hematopoietic stem and progenitor cells, Ex vivo expansion, Differentiation, CXCR4

Chen Dong, Ruiting Wen, Yang Yang, Long Zhao, Li Wang, Lian Duan, Hu Chen, Bin Zhang. Effects of UM171 and SR1 on ex vivo expansion of hematopoietic stem and progenitor cells from different sources[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2020, 10(02): 82-89.

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Figures/Tables 12

References 16

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分组	CD34⁺细胞	CD34⁺ CD38^-细胞	CD34⁺ CD38^- CD45RA^- CD90⁺细胞
未培养组	93.64±1.63	10.19±2.48	1.82±1.61
对照组	52.57±5.98^a	39.31±4.62^a	0.80±0.54
UM171组	80.12±4.83^ab	68.02±7.72^ab	3.71±3.06
SR1组	77.24±6.65^ab	49.81±9.81^abc	1.65±0.83
UM171+SR1组	87.91±4.20^bcd	68.90±9.21^abd	3.93±2.53
F值	50.291	54.634	2.423
P值	< 0.001	< 0.001	0.082

分组	CD34⁺细胞	CD34⁺ CD38^-细胞	CD34⁺ CD38^- CD45RA^- CD90⁺细胞
未培养组	93.64±1.63	10.19±2.48	1.82±1.61
对照组	52.57±5.98^a	39.31±4.62^a	0.80±0.54
UM171组	80.12±4.83^ab	68.02±7.72^ab	3.71±3.06
SR1组	77.24±6.65^ab	49.81±9.81^abc	1.65±0.83
UM171+SR1组	87.91±4.20^bcd	68.90±9.21^abd	3.93±2.53
F值	50.291	54.634	2.423
P值	< 0.001	< 0.001	0.082

分组	总有核细胞	CD34⁺细胞	CD34⁺ CD38^-细胞	CD34⁺CD38^-CD45RA^- CD90⁺细胞
对照组	129.06±21.71	72.47±14.41	532.59±210.08	67.43± 30.84
UM171组	140.68±50.75	121.82±49.59	1037.36±587.09	318.53±147.94
SR1组	147.32±23.20	120.40±15.16	792.11±388.75	201.71±157.55
UM171+SR1组	167.54±69.82	156.97±65.79^a	1249.83±670.19	473.88±356.18^a
F/H值	1.344	8.714	5.000	3.420
P值	0.719	0.033	0.172	0.043

分组	总有核细胞	CD34⁺细胞	CD34⁺ CD38^-细胞	CD34⁺CD38^-CD45RA^- CD90⁺细胞
对照组	129.06±21.71	72.47±14.41	532.59±210.08	67.43± 30.84
UM171组	140.68±50.75	121.82±49.59	1037.36±587.09	318.53±147.94
SR1组	147.32±23.20	120.40±15.16	792.11±388.75	201.71±157.55
UM171+SR1组	167.54±69.82	156.97±65.79^a	1249.83±670.19	473.88±356.18^a
F/H值	1.344	8.714	5.000	3.420
P值	0.719	0.033	0.172	0.043

分组	总有核细胞	CD34⁺细胞	CD34⁺ CD38^-细胞	CD34⁺ CD38^- CD45RA^- CD90⁺细胞
对照组	62.26±19.99	26.69± 9.28	216.19± 59.94	27.55±13.44
UM171组	69.57±25.32	58.38±27.42	543.13±242.33^a	205.13±84.14^a
SR1组	58.58±22.68	52.73±28.87	331.26±101.79	70.40±23.04^b
UM171+SR1组	54.35±22.70	54.58±26.23	435.45±192.72	169.92±70.94^ac
F/H值	0.402	1.773	8.166	10.779
P值	0.753	0.193	0.043	< 0.001

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