Identification of a Distinct Small Cell Population from Human Bone Marrow Reveals Its Multipotency In Vivo and In Vitro

James Wang,Yun Yen,Megan Chang,Jennifer Yoo,Pei-Ju Chu,Monica Lui,Xiaoyu Guo,Nanette H Bishopric

doi:10.1371/journal.pone.0085112

Abstract

Small stem cells, such as spore-like cells, blastomere-like stem cells (BLSCs), and very-small embryonic-like stem cells (VSELs) have been described in recent studies, although their multipotency in human tissues has not yet been confirmed. Here, we report the discovery of adult multipotent stem cells derived from human bone marrow, which we call StemBios (SB) cells. These isolated SB cells are smaller than 6 ìm and are DAPI+ and Lgr5+ (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5). Because Lgr5 has been characterized as a stem cell marker in the intestine, we hypothesized that SB cells may have a similar function. In vivo cell tracking assays confirmed that SB cells give rise to three types of cells, and in vitro studies demonstrated that SB cells cultured in proprietary media are able to grow to 6–25 ìm in size. Once the SB cells have attached to the wells, they differentiate into different cell lineages upon exposure to specific differentiation media. We are the first to demonstrate that stem cells smaller than 6 ìm can differentiate both in vivo and in vitro. In the future, we hope that SB cells will be used therapeutically to cure degenerative diseases.

Highlights

Stem cells have been derived from the inner cell mass, adult tissues [1,2,3,4], and adult somatic cells [5,6]
2.1 SB cells are present in human bone marrow and peripheral blood
It has been suggested that small stem cells, such as spore-like cells [26,27], very-small embryonic-like stem cells (VSELs) [28,29], and blastomere-like stem cells (BLSCs) [30], may exist in all adult tissues

Summary

Introduction

Stem cells have been derived from the inner cell mass (hESCs: human Embryonic Stem Cells), adult tissues [1,2,3,4], and adult somatic cells (iPSs: induced Pluripotent Stem Cells) [5,6]. Unlike hESCs and iPSs, do not undergo teratoma formation [13,14] or immune rejection in autologous transplants. Adult stem cell studies have focused on MSCs (mesenchymal stem cells) [15], which are considered a promising therapeutic approach for many diseases [16,17,18]. They can be isolated from sources such as umbilical cord blood [19] and bone marrow [20], among others [21,22]. Obtaining multipotent or pluripotent adult stem cells that can differentiate into different germ layers is crucial for future cell therapy

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Conclusion