Mouse Dental Pulp Stem Cells Support Human Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells in Vitro

Nakatsuka, Ryusuke; Matsuoka, Yoshikazu; Uemura, Yukari; Sumide, Keisuke; Iwaki, Ryuji; Takahashi, Masaya; Fujioka, Tatsuya; Sasaki, Yutaka; Sonoda, Yoshiaki

doi:10.3727/096368913x674675

Cited by 5 publications

(3 citation statements)

References 46 publications

(73 reference statements)

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“…We investigated the hematopoiesis-supporting properties of BM-derived MSCs obtained from different species. We found that mMSCs support the proliferation and migration of CD34 + hHSPCs in agreement with recent reports demonstrating the expansion of CD34 + hematopoietic cells in the presence of either murine stromal cell lines or mMSC-like cells derived from dental pulps 31 32 . Nonetheless, we observed subtle differences in their capacity to support certain hHSPC subpopulations and to maintain the HSPC polarization by comparing them to those derived from human tissues.…”

Section: Discussionsupporting

confidence: 92%

Phenotypic, Morphological and Adhesive Differences of Human Hematopoietic Progenitor Cells Cultured on Murine versus Human Mesenchymal Stromal Cells

Reichert

Friedrichs

Ritter

et al. 2015

Sci Rep

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Xenogenic transplantation models have been developed to study human hematopoiesis in immunocompromised murine recipients. They still have limitations and therefore it is important to delineate all players within the bone marrow that could account for species-specific differences. Here, we evaluated the proliferative capacity, morphological and physical characteristics of human CD34 + hematopoietic stem and progenitor cells (HSPCs) after co-culture on murine or human bone marrowderived mesenchymal stromal cells (MSCs). After seven days, human CD34 + CD133-HSPCs expanded to similar extents on both feeder layers while cellular subsets comprising primitive CD34 + CD133 + and CD133 + CD34 -phenotypes are reduced fivefold on murine MSCs. The number of migrating HSPCs was also reduced on murine cells suggesting that MSC adhesion influences cellular polarization of HSPC. We used atomic force microscopy-based single-cell force spectroscopy to quantify their adhesive interactions. We found threefold higher detachment forces of human HSPCs from murine MSCs compared to human ones. This difference is related to the N-cadherin expression level on murine MSCs since its knockdown abolished their differential adhesion properties with human HSPCs. Our observations highlight phenotypic, morphological and adhesive differences of human HSPCs when cultured on murine or human MSCs, which raise some caution in data interpretation when xenogenic transplantation models are used.Deciphering the cellular and molecular players involved in the homeostasis of the bone marrow (BM) niches is essential to gain insight into processes of hematopoietic stem and progenitor cell (HSPC) mobilization and homing to improve treatment options for patients with several hematological diseases. The use of various immunodeficient murine models and new imaging techniques, such as two-photon laser-scanning intravital microscopy, has increased our knowledge of mechanisms underlying the egress of HSPCs from, and their homing and lodging into the BM upon mobilization and transplantation, respectively 1,2 . The establishment of co-culture systems based on feeder cell layers (primary cells or cell lines) of human (h) origin has contributed to our understanding of hHSPC biology [3][4][5] . Using

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Section: Discussionsupporting

confidence: 92%

Phenotypic, Morphological and Adhesive Differences of Human Hematopoietic Progenitor Cells Cultured on Murine versus Human Mesenchymal Stromal Cells

Reichert

Friedrichs

Ritter

et al. 2015

Sci Rep

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“…DPSCs have been reported to possess many in vitro characteristics of mesenchymal stem cells (MSCs) with high clonogenicity and MSC marker expression [34][35][36][37][38][39][40] . However, the in vivo stem cell properties and physiological function of DPSCs in adult teeth remain elusive.…”

Section: Mx1 + Ocnpulp Cells Show High Expression Of Dental Pulp Stem...mentioning

confidence: 99%

Mx1-labeled pulp progenitor cells are main contributors to postnatal odontoblasts and pulp cells in murine molars

Yang,

Jeong,

Ortinau

et al. 2024

Preprint

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SUMMARYRegeneration of dentin and odontoblasts from dental pulp stem cells (DPSCs) is essential for permanent tooth maintenance. However, thein vivoidentity and role of endogenous DPSCs in reparative dentinogenesis are elusive. Here, using pulp single-cell analysis before and after molar eruption, we revealed that endogenous DPSCs are enriched inCxcl12-GFP+coronal papilla-like cells withMx1-Cre labeling. TheseMx1+Cxcl12-GFP+cells are long-term repopulating cells that contribute to the majority of pulp cells and new odontoblasts after eruption. Upon molar injury,Mx1+DPSCs localize into the injury site and differentiate into new odontoblasts, formingscleraxis-GFP+andosteocalcin-GFP+dentinal tubules and reparative dentin. Single-cell and FACS analysis showed thatMx1+Cxcl12-GFP+DPSCs are the most primitive cells with stem cell marker expression and odontoblast differentiation. Taken together, our findings demonstrate thatMx1labels postnatal DSPCs, which are the main source of pulp cells and new odontoblasts with reparative dentinogenesisin vivo.

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“…MSCs derived from dental pulp tissue (DP-MSC) differ from the other MSCs because their embryonic origin is the neural crest [ 16 ]. Mouse DP-MSCs have been reported to support in vitro growth of human UCB-HSPCs [ 17 ]. The successful differentiation of MSCs from human iPSCs via a neural crest cell lineage by traditional monolayer cultures has been reported [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells

Zhou,

Cai,

Zhang

et al. 2024

Stem Cell Res Ther

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Background Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. Methods Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. Results The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. Conclusions A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell–cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

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Mouse Dental Pulp Stem Cells Support Human Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells in Vitro

Cited by 5 publications

References 46 publications

Phenotypic, Morphological and Adhesive Differences of Human Hematopoietic Progenitor Cells Cultured on Murine versus Human Mesenchymal Stromal Cells

Phenotypic, Morphological and Adhesive Differences of Human Hematopoietic Progenitor Cells Cultured on Murine versus Human Mesenchymal Stromal Cells

Mx1-labeled pulp progenitor cells are main contributors to postnatal odontoblasts and pulp cells in murine molars

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells

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