Stem cell homing: From physiology to therapeutics

Liesveld, Jane L.; Sharma, Naman; Aljitawi, Omar S.

doi:10.1002/stem.3242

Cited by 147 publications

(117 citation statements)

References 153 publications

(173 reference statements)

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“…In vivo studies have shown that such cell-cell interactions are essential for the migration, mobilization, and maintenance of HSPCs within BM 23 . Additionally, it is hypothesized that the first interaction during the homing of HSPC in BM is with the sinusoidal endothelium 34 . Therefore, our findings that HSPCs migrated more efficiently in BMOs containing a larger network-like structure, as well as the close proximity between the two cell types, suggest that our 3D system mimics essential parts of such cellular interactions found in natural BM 23,34 .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, it is hypothesized that the first interaction during the homing of HSPC in BM is with the sinusoidal endothelium 34 . Therefore, our findings that HSPCs migrated more efficiently in BMOs containing a larger network-like structure, as well as the close proximity between the two cell types, suggest that our 3D system mimics essential parts of such cellular interactions found in natural BM 23,34 . Further investigation of the migration process of HSPCs in BMOs proposed a partial regulation of the CXCL12-CXCR4 signaling pathway, which is known to be the main regulator for human stem cell homing 35 .…”

Section: Discussionmentioning

confidence: 99%

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Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Giger

Hofer

Miljkovic‐Licina

et al. 2021

Preprint

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In many leukemia patients, a poor prognosis is attributed either to the development of chemotherapy resistance by leukemic stem cells (LSCs) or to the inefficient engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM). Here, we build a 3D in vitro model system of bone marrow organoids (BMOs) that recapitulate several structural and cellular components of native BM. These organoids are formed in a high-throughput manner from the aggregation of endothelial and mesenchymal cells within hydrogel microwells. Accordingly, the mesenchymal compartment shows partial maintenance of its self-renewal and multilineage potential, while endothelial cells self-organize into an interconnected vessel-like network. Intriguingly, such a vascular compartment enhances the recruitment of HSPCs in a chemokine ligand/receptor-dependent manner, reminiscent of HSPC homing behavior in vivo. Additionally, we also model LSC migration and nesting in BMOs, thus highlighting the potential of this system as a well accessible and scalable preclinical model for candidate drug screening and patient-specific assays.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Giger

Hofer

Miljkovic‐Licina

et al. 2021

Preprint

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“…The efficacy of sitagliptin, and other potential interventions that target BDMSC and decidual precursor cells [27], in mitigating the risk of adverse pregnancy outcome warrants further evaluation in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…CXCR4 and KIT) and trans-endothelial migration (e.g. ITGA4 and CD82) [27]. However, unlike IC, hPMC also express genes coding for secreted factors implicating in MSC self-renewal and engraftment ( Fig.…”

Section: Characterization Of Hpmc In Midluteal Endometriummentioning

confidence: 99%

Characterization of highly proliferative decidual precursor cells during the window of implantation in human endometrium

Diniz-da-Costa

Kong

Fishwick

et al. 2020

Preprint

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Pregnancy depends on the wholesale transformation of the endometrium, a process driven by differentiation of endometrial stromal cells (EnSC) into specialist decidual cells. Upon embryo implantation, decidual cells impart the tissue plasticity needed to accommodate a rapidly growing conceptus and invading placenta, although the underlying mechanisms are unclear. Here we characterize a discrete population of highly proliferative mesenchymal cells (hPMC) in midluteal human endometrium, coinciding with the window of embryo implantation. Single-cell transcriptomics demonstrated that hPMC express genes involved in chemotaxis and vascular transmigration. Although distinct from resident EnSC, hPMC also express genes encoding pivotal decidual transcription factors and markers, most prominently prolactin. We further show that hPMC are enriched around spiral arterioles, scattered throughout the stroma, and occasionally present in glandular and luminal epithelium. The abundance of hPMC correlated with the in vitro colony-forming unit activity of midluteal endometrium and, conversely, clonogenic cells in culture express a gene signature partially conserved in hPMC. Cross-referencing of single-cell RNA-sequencing data sets indicated that hPMC differentiate into a recently discovered decidual subpopulation in early pregnancy. Finally, we demonstrate that recurrent pregnancy loss is associated with hPMC depletion. Collectively, our findings characterize midluteal hPMC as novel decidual precursors that are likely derived from circulating bone marrow-derived mesenchymal stem/stromal cells and integral to decidual plasticity in pregnancy.

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“…A potential reason for the observed inconsistencies is the heterogeneity of cultured MSCs, which is influenced by the individual donor and tissue of origin, isolation technique, culture environment, and cell passage number (Wilson et al, 2019;Harman et al, 2020). Purposefully manipulating MSCs to improve therapeutic benefits, which by default could result in a more standardized and/or customized secretome, is not a novel idea, but one that has not yet been maximally explored (Liesveld et al, 2020;Ocansey et al, 2020).…”

Section: Manipulated Mscsmentioning

confidence: 99%

Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

Harman

Marx

Walle

2021

Front. Cell Dev. Biol.

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The therapeutic potential of the mesenchymal stromal cell (MSC) secretome, consisting of all molecules secreted by MSCs, is intensively studied. MSCs can be readily isolated, expanded, and manipulated in culture, and few people argue with the ethics of their collection. Despite promising pre-clinical studies, most MSC secretome-based therapies have not been implemented in human medicine, in part because the complexity of bioactive factors secreted by MSCs is not completely understood. In addition, the MSC secretome is variable, influenced by individual donor, tissue source of origin, culture conditions, and passage. An increased understanding of the factors that make up the secretome and the ability to manipulate MSCs to consistently secrete factors of biologic importance will improve MSC therapy. To aid in this goal, we can draw from the wealth of information available on secreted factors from MSC isolated from veterinary species. These translational animal models will inspire efforts to move human MSC secretome therapy from bench to bedside.

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Stem cell homing: From physiology to therapeutics

Cited by 147 publications

References 153 publications

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Characterization of highly proliferative decidual precursor cells during the window of implantation in human endometrium

Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

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