Introduction: Transplantation of the Normal Mammary Gland: Early Evidence for a Mammary Stem Cell

The mammary gland contains adult stem cells that are capable of self-renewal. This population plays an important role in the development of mammary gland and breast cancer pathogenesis. The studies of mammary stem cells are limited due to the difficulty to acquire and expand adult stem cell population in an undifferentiated state. In this study, we developed mammosphere cultures of nulliparous cynomolgus monkeys (Macaca fascicularis; Mf) as a culture system to enrich mammary stem cells. This species has similarity of mammary gland structure as humans including anatomy, developmental stages, and lobule profile of mammary gland. The use of stem cells from primate animals is essential to bridge the knowledge gaps resulting from stem cell research using rodents for clinical trials in human. Small samples of mammary tissues were collected by surgical biopsy; cells were cultured as monolayer and cryopreserved. Cryopreserved cells were cultured into mammospheres, and the expression of markers for mammary stem cells was evaluated using qPCR. Cells were further differentiated with 3D approaches to evaluate morphology and organoid budding. The study showed that mammosphere culture resulted in an increase in the expression of mammary stem cell markers with each passage. The 3D differentiation in matrigel allowed for organoid formation. Mammary gland stem cells have been successfully differentiated which characterized by CSN2 marker expression and differentiation regulators marker STAT5 and GATA3. The results indicate that mammospheres can be successfully developed derived from breast tissue of nulliparous Mf collected via surgical biopsy. As the mammosphere allows for enrichment of mammary stem cell population, the findings also suggest that a 3-dimensional system is efficient as in-vitro model to study mammary stem cells and a useful system to study mammary differentiation in regards to cancer prevention.

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Intraductally administered pegylated liposomal doxorubicin reduces mammary stem cell function in the mammary gland but in the long term, induces malignant tumors

Breast Cancer Research and Treatment ◽

10.1007/s10549-012-2138-x ◽

2012 ◽

Vol 135 (1) ◽

pp. 201-208 ◽

Cited By ~ 11

Author(s):

Yong Soon Chun ◽

Takahiro Yoshida ◽

Tsuyoshi Mori ◽

David L. Huso ◽

Zhe Zhang ◽

...

Keyword(s):

Stem Cell ◽

Mammary Gland ◽

Liposomal Doxorubicin ◽

Cell Function ◽

Malignant Tumors ◽

Pegylated Liposomal Doxorubicin ◽

Mammary Stem Cell ◽

Mammary Stem

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CD24 and CD49f expressions of E14.5 mouse mammary anlagen cells define putative distribution of earlier embryonic mammary stem cell activities

Biochemistry and Cell Biology ◽

10.1139/bcb-2017-0177 ◽

2018 ◽

Vol 96 (5) ◽

pp. 539-547 ◽

Cited By ~ 1

Author(s):

Jiazhe Song ◽

Fangrong Ding ◽

Song Li ◽

Wenzhe Li ◽

Ning Li ◽

...

Keyword(s):

Stem Cell ◽

Mammary Gland ◽

Cell Population ◽

Cell Biology ◽

Cell Activity ◽

Mammary Stem Cell ◽

Flow Cytometry Analysis ◽

Large Numbers ◽

Stem Cell Activity ◽

Mammary Stem

Stem cell biology offers promise for understanding the origins of the mammary gland. However, the distribution of mammary stem cell (MaSC) activities at earlier embryonic stages has not been fully identified. The markers for sorting adult MaSC, CD24, CD29, and CD49f have been applied to analyze fetal MaSCs. Here we explored mammary anlagen MaSCs by investigating the expression of CD24 and CD49f. According to the comparative analysis between adult mammary gland and fetal mammary anlagen, we found that fetal mouse mammary anlagen may possess a high percentage of potential MaSCs. Flow cytometry analysis revealed 2 distinct mammary anlagen populations: Lin–CD24med and Lin–CD24high. Sphere-forming and mammary repopulating assays confirmed that the stem cell activity of E14.5 mouse mammary anlagen was restricted to the Lin–CD24med cell population. Furthermore, CD24med mammary anlagen cells were separated into Lin–CD24medCD49f+ and Lin–CD24medCD49f– populations and identified, respectively. The results proved that the mammary anlagen Lin–CD24medCD49f+ cell population possesses more stem cell activities than the Lin–CD24medCD49f– cell population. However, a limited numbers of stem cells and large numbers of stromal cells were identified in mammary anlagen in the Lin–CD24med cell population.

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