Study of stem cell homing &amp; self-renewal marker gene profile of ex vivo expanded human CD34+ cells manipulated with a mixture of cytokines &amp; stromal cell-derived factor 1

Kode, Jyoti; Khattry, Navin; Bakshi, Ashish; Amrutkar, Vasanti; Bagal, Bhausaheb; Karandikar, Rohini; Rane, Pallavi; Fujii, Nobutaka; Chiplunkar, Shubhada V.

doi:10.4103/ijmr.ijmr_1319_15

Cited by 3 publications

(5 citation statements)

References 34 publications

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“…To test stem cell implantation ability, Liang et al [28] injected young or old BM cells into congenic mice, and they found that the homing efficiency of old mouse was approximately three-fold lower than that of young mouse. Some specific genes have been demonstrated to be crucial in regulating HSC repopulation, such as Cdc42, Ccr9, Gnrh2, and Lep [29,30]. CD44 is critical in the maintenance and migration of HSCs [31], and the absence of CD44 in neonatal BM was shown to enhance the longterm engraftment potential of HSCs.…”

Section: Homing and Engraftmentmentioning

confidence: 99%

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Zhang

et al. 2020

J Hematol Oncol

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Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed from various perspectives to illustrate the potential mechanisms of HSC aging; however, the detailed molecular mechanisms remain unclear, blocking further exploration of aged HSC rejuvenation. To determine how aged HSC defects occur, we provide an overview of differences in the hallmarks, signaling pathways, and epigenetics of young and aged HSCs as well as of the bone marrow niche wherein HSCs reside. Notably, we summarize the very recent studies which dissect HSC aging at the single-cell level. Furthermore, we review the promising strategies for rejuvenating aged HSC functions. Considering that the incidence of many hematological malignancies is strongly associated with age, our HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance.

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Section: Homing and Engraftmentmentioning

confidence: 99%

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Zhang

et al. 2020

J Hematol Oncol

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“…In contrast, hCXCL12 Q48K displayed a slower release, demonstrating a stronger heparin binding. This variant remained longer in the hydrogel compared to wild type hCXCL12, where it could serve as a homing factor for the recruited stem and progenitor cells before its delayed release. , …”

Section: Discussionmentioning

confidence: 90%

“…This variant remained longer in the hydrogel compared to wild type hCXCL12, where it could serve as a homing factor for the recruited stem and progenitor cells before its delayed release. 51,52 To test whether progenitor cells, which are addressed in vivo, would react to the loaded hydrogels, we used eEPCs in migration studies. We found a significantly higher migration effect of the gels loaded with the low-affinity K24/K27/R41/ R47A mutant.…”

Section: ■ Discussionmentioning

confidence: 99%

Modulation of Human CXCL12 Binding Properties to Glycosaminoglycans To Enhance Chemotactic Gradients

Spiller

Panitz

Limasale

et al. 2019

ACS Biomater. Sci. Eng.

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Controlled release of active biomolecules is an attractive approach to modulate chemotactic gradients and accordingly the recruitment of cells, e.g. endothelial progenitor cells to improve wound healing or stimulate angiogenesis after myocardial infarction. Here, we developed variants of hCXCL12, also named stromal cell-derived factor 1α, a chemokine that activates the CXCR4 and consequently recruits tissue specific stem and progenitor cells. hCXCL12 variants were designed to bind to glycosaminoglycans (GAGs) with different affinities in order to modulate its release. Sixteen analogs were recombinantly produced, characterized, and tested for their GAG-binding property. The most promising variants hCXCL12 K24/K27/R41/R47A and hCXCL12 Q48K were used for release studies from starPEG-heparin-hydrogels. The reduced GAG affinity led to a fast release of hCXCL12 K24/K27/R41/R47A, whereas hCXCL12 Q48K was slowly released over 2 weeks due to its increased binding strength compared to wild type hCXCL12. Migration of Jurkat cells and early endothelial progenitor cells was proven to demonstrate the applicability of the approach to endogenously CXCR4 expressing cell types. Thus, this work offers new options for enhancing chemotactic hCXCL12 gradients by a combination of native and modified hCXCL12 variants to improve and prolong the recruitment of CXCR4-positive stem and progenitor cells to injured sites.

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“…Overcoming this limitation, several studies have been done to find the best strategies for UCB‐HSC expansion over the last decades. Almost all strategies have a general consensus to use recombinant human (rhu) growth factors such as stem cell factor (SCF), thrombopoietin (TPO), and fms‐like tyrosine kinase 3 ligand (Flt3L) …”

Section: Introductionmentioning

confidence: 99%

“…Almost all strategies have a general consensus to use recombinant human (rhu) growth factors such as stem cell factor (SCF), thrombopoietin (TPO), and fms-like tyrosine kinase 3 ligand (Flt3L). 1 CD34 + HSC/MSC coculture system in presence of ex vivo growth factors is increasingly being used as a method for UCB-HSC expansion. 2 It can mimic the bone marrow HSC niche.…”

Section: Introductionmentioning

confidence: 99%

Comparison of cord blood CD34 + stem cell expansion in coculture with mesenchymal stem cells overexpressing SDF‐1 and soluble /membrane isoforms of SCF

Ajami

Soleimani

Abroun

et al. 2019

J of Cellular Biochemistry

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Aim Umbilical cord blood hematopoietic stem cells (UCB HSCs) have been considered for the treatment of hematological malignancies due to their noninvasive collection, greater capacity of expansion, and remarkable tolerance for HLA mismatch in transplantation. On the other hand, the most considerable limitation of these cells is their inadequate amount of CD34 + HSCs which leads to delayed engraftment. The aim of this study was the expansion of CD34 + HSCs by coculturing with mesenchymal stem cells (MSCs) overexpressing stromal cell‐derived factor‐1, soluble and membrane isoforms of stem cell factor (sSCF/mSCF). Keeping structure and function of overexpressed cytokines by MSCs was expected which could beneficially affect the CD34 + HSC expansion. Methods MSCs and CD34 + HSCs were isolated from UCB mononuclear cells. UCB MSCs were nucleofected with one or more of sSCF, mSCF, and SDF‐1 expression vectors. Isolated CD34 + HSCs were then cocultured with nucleofected MSCs in 10 groups in culture medium containing TPO and Flt3L with or without SCF (3F or 2F groups). Then the CD34 + HSCs numeration, clonogenic capacity, and transcriptional levels of well‐known HSCs regulatory and stemness genes (CXCR4, HOXB4, BMI1, and SALL4) were assessed following coculture with modified MSCs. Results CD34 + HSCs which expanded on MSCs overexpressing mSCF/sSCF/SDF‐1 in the 3F group showed the most significant increase in the expansion (4.73 ± 0.26 fold), clonogenic capacity (5.3 ± 0.25 fold) and also transcriptional levels of CXCR4, HOXB4, and BMI1 (3.49 ± 0.13, 9.49 ± 0.78, and 11.6 ± 0.9 fold), respectively ( P < 0.05). Conclusion Overexpression of SCF and SDF‐1 by UCB MSCs in coculture system has efficient effect on UCB HSCs expansion. Furthermore nucleofected MSC overexpressing either sSCF/mSCF or mSCF/ sSCF /SDF‐1 could substitute the rhu SCF in HSC expansion culture medium.

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Study of stem cell homing & self-renewal marker gene profile of ex vivo expanded human CD34+ cells manipulated with a mixture of cytokines & stromal cell-derived factor 1

Cited by 3 publications

References 34 publications

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Modulation of Human CXCL12 Binding Properties to Glycosaminoglycans To Enhance Chemotactic Gradients

Comparison of cord blood CD34 + stem cell expansion in coculture with mesenchymal stem cells overexpressing SDF‐1 and soluble /membrane isoforms of SCF

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