Charactistics and Biological Models of MSCs, iPSCs

Author: AcceGen R&D Team

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Mesenchymal stem cells (MSCs) and induced-pluripotent stem cells (iPSCs) are both valuable tools for research and high-value research object. MSCs have great potential in assisting organ regeneration and transplantation therapy. And iPSCs are an ideal model and tool in laboratory research, clinical trial and treatment in various areas. Learning more information about MSCs and iPSCs is helpful for researchers and clinical practitioners.

What are Stem Cells?

Stem cells refer to undifferentiated or partially differentiated cells that exist in multicellular organisms. It can self-replication for proliferation and differentiate into specialized cells with specific physiological functions[1]. Stem cells have two core properties: self-renewal capacity and differentiation potency. Self-renewal capacity refers to the ability that maintains the population of stem cells through the asymmetric cell division mechanism of stem cells and the protective effects of telomerase (Figure.1) [2; 3]. Differentiation potency refers to the measurement of the differentiation potential of stem cells. Based on potency, stem cells can be divided into totipotent, pluripotent, multipotent, oligopotent, and unipotent stem cells[4]. Two main types of stem cells are embryonic stem cells (ESCs) and adult stem cells. ESCs mainly present and play a key role in embryonic[5]. Adult stem cells are mainly present in children and adults and play fundamental roles in physiological activities[6].

Mesenchymal Stem Cells (MSCs)

Introduction

Mesenchymal stem cells (MSCs) are also known as mesenchymal stromal cells or medicinal signaling cells, and they are a type of adult stem cells[7; 8; 9]. MSCs mainly sourced from stromal, but they also can be isolated from various organs or tissue, such as bone marrow, placenta, adipose tissue, lung, bone marrow and blood, teeth, and Wharton’s jelly from the umbilical cord[10; 11]. MSCs belong to multipotent stromal cells that can differentiate into various cells, including osteoblasts, chondrocytes, myocytes, and adipocytes[12].

The characteristics of MSCs mainly include differentiation capacity, immune regulation, and antimicrobial properties. Differentiation capacity is the basic guarantee of MSCs as a type of stem cells become the supporter of organs and tissue survival[10]. Regarding immune regulation, MSCs can produce a variety of immune factors and affect various innate and specific immune cells[13; 14]. And then about antibacterial ability, MSCs can produce a variety of antibacterial peptides that enables MSCs to have broad-spectrum antibacterial activity[15].

Culture Protocol

MSCs can be isolated from various organs and tissue, but the traditional source is bone marrow. And in laboratory research, animal bone marrow is the most common source for researchers to obtain MSCs. Take the isolation and culture protocol of MSCs from mice as an example[16]. The bone marrow aspiration mix is harvested from the tibia and femoral marrow compartments and then cultured in DMED (10% FBS, 37℃, and 5% CO2). Suspension cells that did not adhere successfully will be carefully removed after 3 hours of culture. Primary culture can be purified by trypsin digestion and re-plating, and the purified MSCs cultures are successfully obtained after three weeks of culture.

Induced pluripotent stem cells (iPSCs)

Introduction

Induced pluripotent stem cells (iPSCs) are stem cells that can be directly generated from a somatic cell. Construction technology of iPSCs was developed by Shinya Yamanaka and his team in 2006. Four specific factors (c-Myc, Oct3/4, Sox2, and Klf4, also known as Yamanaka factors) as encoding transcription factors can convert somatic cells into pluripotent stem cells[17]. And Yamanaka was awarded the 2012 Nobel Prize with another scientist (John Gurdon) for the discovery that mature cells can be reprogrammed to become pluripotent. As totipotent stem cells, iPSCs are highly similar to ESCs except for different sources. But there are some subtle differences between iPSCs and ESCs. For example, DNA methylation traces characteristic of some somatic cells are preserved during epigenetic reprogramming.

iPSCs is a valuable tool and model in multiple fields research, including drug development[18], organ synthesis[19], tissue repair[20], cardiomyocytes[21], clinical trial[22], anti-aging properties[23], etc. The production of iPSCs experienced several technical iterations, the first (2006)[17] and the second (June 2007)[24] generation are both based on mouse. The generation of human iPSCs was firstly reported in November 2007 from human fibroblasts[25], and gradually, there were iPSCs generated from other cell types.

Culture Protocol

The culture methods of iPSCs can be divided into with or without trophoblast. In the traditional cultivation systems with trophoblast, the culture medium is mainly DMEM with fibroblast growth factor (bFGF) and serum (or non-serum substitution), and the trophoblast mainly refers to cell cycle arrested mouse embryonic fibroblasts (MEF). Trophoblast cells can provide growth factors, cytokine, and nutrients to iPSCs[26; 27]. To improve the instability of the cultivation system with trophoblast due to the complex components and excessive animal-derived components, the cultivation systems of iPSCs were also iterated during the past decades[28], gradually removing trophoblasts and animal-derived components that require MEFs from the culture system.

Application of Biological Model Based on MSCs and iPSCs

The immune regulation function of MSCs has high application value in regenerative therapies. Applying MSCs treatment before allogeneic organ transplantation or regenerative transplantation can improve organ survival rate and efficacy.

MSCs can be obtained conveniently from the induced differentiation of iPSCs in vitro. Sun, et al. successfully enhance the efficacy of cell-based therapy in tissue regeneration through repeated intravenous administration of human-iPSCs-induced MSCs (hiPSCs-MSCs) [29]. They establish a mouse model of hind-limb ischemia and give intravenous administration of hiPSCs-MSCs during the hiPSCs-MSCs muscle transplant treatment. According to their results, compared with control and single dose, repeat dose shows better treatment effect, The splenic regulatory T cells (Tregs) activation is increased, expression of NK cells is downregulated, the polarization of M2 macrophages and blood perfusion in the ischemic area is improved.

Conclusion

As stem cells, MSCs and iPSCs are both hot spots in basic and clinical research. MSCs are potential targets for various diseases due to their immunomodulatory abilities, and iPSCs are potential pathways for cell therapy and in vitro organ culture. But the exploration of stem cells is often accompanied by ethical controversies. And this is one of the core issues that need to be solved for stem cells to move from the laboratory to the clinic.

Where to Get MSCs, iPSCs for Your Research?

AcceGen offers a wide range of high-quality human/animal stem cells, including MSCs, iPSCs, ESCs, Adult Stem Cells, and Tumor Stem Cells. These cell lines provide you with a convenient means to research. To get more information, please refer to: Stem Cells.

It is our pleasure to help relative researches to move forward. All the products of AcceGen are strictly comply with international standards. For more detailed information, please visit our product portfolio or contact inquiry@accegen.com.

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