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Review
. 2024 Jul 30:12:1414156.
doi: 10.3389/fbioe.2024.1414156. eCollection 2024.

The Phoenix of stem cells: pluripotent cells in adult tissues and peripheral blood

Affiliations
Review

The Phoenix of stem cells: pluripotent cells in adult tissues and peripheral blood

Ranieri Cancedda et al. Front Bioeng Biotechnol. .

Abstract

Pluripotent stem cells are defined as cells that can generate cells of lineages from all three germ layers, ectoderm, mesoderm, and endoderm. On the contrary, unipotent and multipotent stem cells develop into one or more cell types respectively, but their differentiation is limited to the cells present in the tissue of origin or, at most, from the same germ layer. Multipotent and unipotent stem cells have been isolated from a variety of adult tissues, Instead, the presence in adult tissues of pluripotent stem cells is a very debated issue. In the early embryos, all cells are pluripotent. In mammalians, after birth, pluripotent cells are maintained in the bone-marrow and possibly in gonads. In fact, pluripotent cells were isolated from marrow aspirates and cord blood and from cultured bone-marrow stromal cells (MSCs). Only in few cases, pluripotent cells were isolated from other tissues. In addition to have the potential to differentiate toward lineages derived from all three germ layers, the isolated pluripotent cells shared other properties, including the expression of cell surface stage specific embryonic antigen (SSEA) and of transcription factors active in the early embryos, but they were variously described and named. However, it is likely that they are part of the same cell population and that observed diversities were the results of different isolation and expansion strategies. Adult pluripotent stem cells are quiescent and self-renew at very low rate. They are maintained in that state under the influence of the "niche" inside which they are located. Any tissue damage causes the release in the blood of inflammatory cytokines and molecules that activate the stem cells and their mobilization and homing in the injured tissue. The inflammatory response could also determine the dedifferentiation of mature cells and their reversion to a progenitor stage and at the same time stimulate the progenitors to proliferate and differentiate to replace the damaged cells. In this review we rate articles reporting isolation and characterization of tissue resident pluripotent cells. In the attempt to reconcile observations made by different authors, we propose a unifying picture that could represent a starting point for future experiments.

Keywords: SSEA3/4; VSELs; dedifferentiation; mesenchymal stem cells; muse cells; pluripotent genes; very small embryonic like cells.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Generation of dedifferentiated adipose-derived cells (DFATs). Multipotent or pluripotent dedifferentiated cells are obtained depending on the culture conditions. Multipotent cells are derived from purified adipocytes isolated by “ceiling” culture. Pluripotent cells are obtained by cultures of bulk cells obtained by adipose digestion.
FIGURE 2
FIGURE 2
Proposed correlation between Primordial gem cells, VSELs, and VSEL progeny. Modified from Ratajczak et al. (2019).
FIGURE 3
FIGURE 3
Representative anti-RFP immunostaining of the hard callus and the knee regions from a fractured mouse tail injected with RFP labelled CH cells. Histology sections of the callus formed 24 days after osteotomy (A) and of the knee articular cartilage damaged by the insertion of the fixation device (B). The corresponding regions of the contralateral paw of the same mouse are shown in (C,D). Black arrows indicate osteoblasts (A,C) and articular chondrocytes (C,D). CH cells homing and differentiation was observed in the damaged tissues but not in the “healthy” paw. Scale bar 100 μm. Modified from Lo Sicco et al. (2015).
FIGURE 4
FIGURE 4
A unifying picture of pluripotent stem cells development to terminally differentiated cells in mammalian adult tissues. The picture is based on contributions to the literature made by different authors. Additional experiments may prove that some parts are wrong or need substantial adjustments. However, we believe that the picture could be a good starting point for future experiments.

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