• BMB Reports
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• v.57 no.8
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• pp.352-362
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• 2024

Hematopoietic stem cell transplantation (HSCT) remains an indispensable therapeutic strategy for various hematological diseases. This review discusses the pivotal role of bone marrow (BM) niches in influencing the efficacy of HSCT and evaluates the current animal models, emphasizing their limitations and the need for alternative models. Traditional animal models, mainly murine xenograft, have provided significant insights, but due to species-specific differences, are often constrained from accurately mimicking human physiological responses. These limitations highlight the importance of developing alternative models that can more realistically replicate human hematopoiesis. Emerging models that include BM organoids and BM-on-a-chip microfluidic systems promise enhanced understanding of HSCT dynamics. These models aim to provide more accurate simulations of the human BM microenvironment, potentially leading to improved preclinical assessments and therapeutic outcomes. This review highlights the complexities of the BM niche, discusses the limitations of current models, and suggests directions for future research using advanced model systems.

• BMB Reports
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• v.53 no.2
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• pp.65-73
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• 2020

Life expectancy has dramatically increased around the world over the last few decades, and staying healthier longer, without chronic disease, has become an important issue. Although understanding aging is a grand challenge, our understanding of the mechanisms underlying the degeneration of cell and tissue functions with age and its contribution to chronic disease has greatly advanced during the past decade. As our immune system alters with aging, abnormal activation of immune cells leads to imbalance of innate and adaptive immunity and develops a persistent and mild systemic inflammation, inflammaging. With their unique therapeutic properties, such as immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs) have been considered to be a promising source for treating autoimmune disease or as anti-aging therapy. Although direct evidence of the role of MSCs in inflammaging has not been thoroughly studied, features reported in senescent MSCs or the aging process of MSCs are associated with inflammaging; MSC niche-driven skewing of hematopoiesis toward the myeloid lineage or oncogenesis, production of pro-inflammatory cytokines, and weakening their modulative property on macrophage polarization, which plays a central role on inflammaging development. This review explores the role of senescent MSCs as an important regulator for onset and progression of inflammaging and as an effective target for anti-aging strategies.

• BMB Reports
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• v.56 no.1
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• pp.2-9
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• 2023

Hair follicles in the skin undergo cyclic rounds of regeneration, degeneration, and rest throughout life. Stem cells residing in hair follicles play a pivotal role in maintaining tissue homeostasis and hair growth cycles. Research on hair follicle aging and age-related hair loss has demonstrated that a decline in hair follicle stem cell (HFSC) activity with aging can decrease the regeneration capacity of hair follicles. This review summarizes our understanding of how age-associated HFSC intrinsic and extrinsic mechanisms can induce HFSC aging and hair loss. In addition, we discuss approaches developed to attenuate ageassociated changes in HFSCs and their niches, thereby promoting hair regrowth.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.45 no.4
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• pp.415-422
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• 2019

Human epidermal stem cells(ESCs) residing in the basement membrane of the skin have an important role in maintenance of skin homeostasis of epidermal layer. Although, ESCs provide new cells to repair damaged tissue in response to tissue injury, subsets of stem cells remain in the quiescent state protected from differentiation and senescence for prolonged survivals. In this perspective, the stem cell niche, which is specific microenvironment composed of niche cells and an extracellular matrix(ECM), supplies the relevant signal to save stem cells from microenvironmental damages. The expression of stemness marker on the surface of ESCs contributes to the attachment on their ECM of the basement membrane, which lead to growth potential and apoptotic resistance against environmental stimuli. In this study, we observed that UV irradiation, a major factor of environmental stimuli, reduced the expression of α2, β1 and α6 integrin in ESCs. Rhus Semialata M extract(RSE) showed inhibitory effect on the UVB-induced reduction of integrin expression. Furthermore, RSE could upregulate the expression of Col-IV and Laminin, which contribute to the attachment of ESCs. These results indicated that RSE could be a potent ingredient for the protection of ESCs from UV irradiation by increasing the expression of integrin and substrate ECM components at their niche.

• BMB Reports
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• v.48 no.8
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• pp.427-428
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• 2015

Despite high interests on microenvironmental regulation of leukemic cells, little is known for bone marrow (BM) niche in leukemia patients. Our recent study on BMs of acute myeloid leukemia (AML) patients showed that the mesenchymal stromal cells (MSCs) are altered during leukemic conditions in a clinical course-dependent manner. Leukemic blasts caused reprogramming of transcriptomes in MSCs and remodeling of niche cross-talk, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemo-resistance. Notably, differences in BM stromal remodeling were correlated to heterogeneity in subsequent clinical courses of AML, i.e., low numbers of mesenchymal progenitors at initial diagnosis were correlated to complete remission for 5-8 years, and high contents of mesenchymal progenitor or MSCs correlated to early or late relapse, respectively. Thus, stromal remodeling by leukemic cell is an intrinsic part of leukemogenesis that can contribute to the clonal dominance of leukemic cells over normal hematopoietic cells, and can serve as a biomarker for prediction of prognosis. [BMB Reports 2015; 48(8): 427-428]

• Development and Reproduction
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• v.25 no.4
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• pp.313-319
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• 2021

Hub cells comprise a niche for germline stem cells and cyst stem cells in the Drosophila testis. Hub cells arise from common somatic gonadal precursors in embryos, but the mechanism of their specification is still poorly understood. Here we find that RNA binding proteins Lin28 and Imp mediate transcript stability of Bowl, a known hub specification factor; Bowl transcripts were reduced in the testis of Lin28 and Imp mutants, and also when RNA-mediated interference against Lin28 or Imp was expressed in hub cells. In tissue culture Luciferase assays involving the Bowl 3'UTR, stability of Luc reporter transcripts depended on the Bowl 3'UTR and required Lin28 and Imp. Our findings suggest that proper Bowl function during hub cell specification requires Lin28 and Imp in the testis hub cells.

• Journal of International Society for Simulation Surgery
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• v.4 no.1
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• pp.1-8
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• 2017

In the field of tissue engineering, researches have been actively conducted to regulate stem cell fate by understanding the interaction between cell and materials. This approach is expected as a promising therapeutic method in the future medicine by utilizing differentiation of stem cells into desired cells or tissues using biomaterial. For this regenerative medicine, there exist lots of attempts to construct optimized structures of various shapes and sizes that can regulate the stem cell fate. In this review, we will empathize the topographic effect as stem cell niche on the mesenchymal stem cell (MSC) response (cell attachment, proliferation, and differentiation) according to the shape and size of the structure of the substrates, and comprehensively analyze the importance and the effect of shape and size of the surface topography.

• International Journal of Stem Cells
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• v.15 no.1
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• pp.104-111
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• 2022

Many of early findings regarding intestinal stem cells (ISCs) and their niche in the human intestine have relied on colorectal cancer cell lines and labor-intensive and time-consuming mouse models. However, these models cannot accurately recapitulate the physiologically relevant aspects of human ISCs. In this study, we demonstrate a reliable and robust culture method for 3D expanding intestinal spheroids (InS^exp) mainly comprising ISCs and progenitors, which can be derived from 3D human intestinal organoids (HIOs). We did functional chararcterization of InS^exp derived from 3D HIOs, differentiated from human pluripotent stem cells, and optimization culture methods. Our results indicate that InS^exp can be rapidly expanded and easily passaged, and show enhanced growth rates via WNT pathway activation. InS^exp are capable of exponential cell expansion and cryopreservation. Furthermore, in vitro-matured HIO-derived InS^exp proliferate faster than immature HIO-derived InS^exp with preservation of the parental HIO characteristics. These findings may facilitate the development of scalable culture systems for the long-term maintenance of human ISCs and provide an alternative platform for studying ISC biology.

• BMB Reports
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• v.42 no.5
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• pp.245-259
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• 2009

The process by which adult neural stem cells generate new and functionally integrated neurons in the adult mammalian brain has been intensely studied, but much more remains to be discovered. It is known that neural progenitors progress through distinct stages to become mature neurons, and this progression is tightly controlled by cell-cell interactions and signals in the neurogenic niche. However, less is known about the cell-intrinsic signaling required for proper progression through stages of adult neurogenesis. Techniques have recently been developed to manipulate genes specifically in adult neural stem cells and progenitors in vivo, such as the use of inducible transgenic mice and viral-mediated gene transduction. A critical mass of publications utilizing these techniques has been reached, making it timely to review which molecules are now known to play a cell-intrinsic role in regulating adult neurogenesis in vivo. By drawing attention to these isolated molecules (e.g. Notch), we hope to stimulate a broad effort to understand the complex and compelling cascades of intrinsic signaling molecules important to adult neurogenesis. Understanding this process opens the possibility of understanding brain functions subserved by neurogenesis, such as memory, and also of harnessing neural stem cells for repair of the diseased and injured brain.

• Anatomy and Cell Biology
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• v.56 no.1
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• pp.94-108
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• 2023

Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer. Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.