Nasal Turbinate Mesenchymal Stromal Cells Preserve Characteristics of Their Neural Crest Origin and Exert Distinct Paracrine Activity.

Hyun-Jee Kim,Il-Hoan Oh,Sung-Won Kim,Sungho Shin,Yunhee-Kim Kwon,Chan-Kwon Jung,Sun-Ung Lim,Dae-Won Lee,Seon-Yeong Jeong,Jiyeon Kang,Cheolju Lee

doi:10.3390/jcm10081792

Abstract

The sources of mesenchymal stromal cells (MSCs) for cell therapy trials are expanding, increasing the need for their characterization. Here, we characterized multi-donor, turbinate-derived MSCs (TB-MSCs) that develop from the neural crest, and compared them to bone marrow-derived MSCs (BM-MSCs). TB-MSCs had higher proliferation potential and higher self-renewal of colony forming cells, but lower potential for multi-lineage differentiation than BM-MSCs. TB-MSCs expressed higher levels of neural crest markers and lower levels of pericyte-specific markers. These neural crest-like properties of TB-MSCs were reflected by their propensity to differentiate into neuronal cells and proliferative response to nerve growth factors. Proteomics (LC–MS/MS) analysis revealed a distinct secretome profile of TB-MSCs compared to BM and adipose tissue-derived MSCs, exhibiting enrichments of factors for cell-extracellular matrix interaction and neurogenic signaling. However, TB-MSCs and BM-MSCs exhibited comparable suppressive effects on the allo-immune response and comparable stimulatory effects on hematopoietic stem cell self-renewal. In contrast, TB-MSCs stimulated growth and metastasis of breast cancer cells more than BM-MSCs. Altogether, our multi-donor characterization of TB-MSCs reveals distinct cell autonomous and paracrine properties, reflecting their unique developmental origin. These findings support using TB-MSCs as an alternative source of MSCs with distinct biological characteristics for optimal applications in cell therapy.

Highlights

Mesenchymal stromal cells (MSCs) are non-hematopoietic adherent cell populations with multi-lineage differentiation potential towards diverse types of tissues, including bone, cartilage, vessels, and neuron-like cells [1,2,3], and exhibits common surface phenotypes [4]
To compare MSCs derived from the nasal turbinate (TB-MSCs) with bone marrowderived MSCs (BM-MSCs), and to control for individual variation, we collected each tissue-source of MSCs from multiple donors at similar ages and compared their biological properties
turbinate-derived MSCs (TB-MSCs) exhibited a delay in replicative senescence; TB-MSCs continued to grow beyond passage 16, whereas BM-MSCs reached growth arrest after 11–13 passages (Figure 1D)

Summary

Introduction

Mesenchymal stromal cells (MSCs) are non-hematopoietic adherent cell populations with multi-lineage differentiation potential towards diverse types of tissues, including bone, cartilage, vessels, and neuron-like cells [1,2,3], and exhibits common surface phenotypes [4]. Cell therapeutic trials utilizing ex vivo expanded MSCs are increasing, and their potential within a wide range of applications is being explored. These include the regeneration of damaged cardiovascular [5], neural [6], and muscular–skeletal tissues [7,8,9,10]; the suppression of allogenic immune reactions [11,12], and facilitation of hematopoietic engraftment [13,14] or suppression of graft versus host diseases [15,16]. Accumulating studies have shown that the heterogeneity of MSCs can cause a difference in the biological properties and cell therapeutic outcomes [20,21,22,23,24]

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Conclusion