Characteristics and Applications of Bone Marrow Mesenchymal Stem Cells

Introduction

What are Stem Cells?

Stem cells refer to undifferentiated or partially differentiated cells in multicellular organisms. Stem cells can replicate indefinitely and differentiate into different types of cells with various functions [1]. The research of stem cells originated in the 1960s, Ernest McCulloch from the University of Toronto and James Till from the Ontario Cancer Institute identified the key properties of stem cells [2, 3]. According to the classic definition of stem cells, it needs to have the following two core properties, namely self-renewal capacity and differentiation potency. Self-renewal capacity can maintain the stem cells population, which depends on the asymmetric cell division mechanism and the protective effects of telomerase (Figure.1) [4, 5]. Potency refers to the differentiation potential of stem cells. Based on potency, stem cells can be divided into totipotent, pluripotent, multipotent, oligopotent, and unipotent stem cells [6].

There are two main types of stem cells, embryonic stem cells (ESCs) and adult stem cells. ESCs mainly present in embryonic development and play a central role [7]. Adult stem cells have various members, which present in children and adults and play fundamental roles in the maintenance of life activities [8]. Besides, ordinary adult cells can be artificially reprogrammed and become stem cells, which are named induced pluripotent stem cells (IPSCs) [9]. Stem cells also have some clinical therapeutic applications, the mature application, of course, is mainly bone marrow transplantation in response to leukemia [10]. And there is also a lot of controversy of the clinical application of stem cells, especially the application of embryonic stem cells involves complex ethical disputes [11].

Mesenchymal Stem Cells (MSCs) – What they do in human body?

Mesenchymal stem cells (MSCs) are a type of adult stem cells, it is also known as mesenchymal stromal cells or medicinal signaling cells [12-14]. MSCs are multipotent stromal cells, which can differentiate into various cells including osteoblasts, chondrocytes, myocytes and adipocytes [15]. MSCs mainly sourced from stroma and can be isolated from various tissues, including bone marrow, placenta, adipose, lung, blood, teeth as well as Wharton’s jelly from the umbilical cord  [16, 17].

The functions of MSCs mainly include differentiation capacity, immune regulation and antimicrobial properties. Differentiation capacity indicates the identity of MSCs stem cells and makes it become the basis for maintaining organ and tissue survival [16]. MSCs are also involved in immunomodulatory processes. MSCs can affect a variety of innate and specific immune cells and can produce a variety of immune factors [18, 19]. And the antibacterial ability of MSCs mainly comes from their ability to produce a variety of antibacterial peptides, which enables MSCs to have broad-spectrum antibacterial activity [20].

Bone Marrow Mesenchymal Stem Cells

The original source of MSCs is bone marrow, but it can be isolated from various organs and tissue. In the practical application of MSCs, bone marrow-derived MSCs are sometimes irreplaceable, but because of the difficulty of extraction, MSCs from other sources can sometimes be used as a substitute [21]. MSCs isolated from different locations have different cell surface markers and lineage differentiation to facilitate the correct functioning of MSCs in different locations. Meanwhile, there are also some differences in the separation method of MSCs from different locations [22].

Culture protocols: how to isolate Bone Marrow-derived MSCs from different sources?

As the original source of MSCs, positive surface markers of bone marrow MSCs (bmMSCs) include SH2, SH3, CD29, CD44, CD49e, CD71, CD73, CD90, CD105, CD106, CD166, CD120a, and CD124, negative markers include CD34, CD45, CD19, CD3, CD31, CD11b, and HLA-DR[22]. The isolation of bmMSCs from humans mainly depends on Ficoll density gradient centrifugation [23]. But in laboratory research, animals are a safer and simpler source, therefore the isolation, extraction, and culture methods of bmMSCs based on the mouse model will be briefly introduced[24]. The bone marrow aspiration mix is harvested from the tibia and femoral marrow compartments, and then the aspiration is cultured in DMED with 10% FBS in the culture environment with 37℃ and 5% CO2. After 3 hours of adherent culturing, suspension cells that did not adhere successfully will be carefully removed. Primary cultures can be purified by the operation of trypsin digestion and re-plating, and finally, the purified bmMSCs cultures are successfully obtained after three weeks.

Applications of Bone Marrow Mesenchymal Stem Cells

Bones are living tissues which are being constantly broken down and replaced. Osteoporosis will cause bones to become weak and brittle. With the osteoporosis, the formation of new bone cannot keep up with the removal of old bone. Zhao et al. identify that bmMSCs can help improve osteoporosis [25]. They isolate bmMSCs from the bone marrow of rats and then extract the MSCs-derived exosomes (MSC-Exo). After co-culture of MSC-Exo and osteoblast cell line hFOB 1.19, they analyzed the gene expression and protein that related to osteoporosis of the cell line and the antigenic markers present in MSC-Exo. They identify that the surface markers of bmMSCs are present in MSC-Exo, and find that MSC-Exo can promote the proliferation and cell cycle of the hFOB 1.19 cell line. And then, they confirm the mechanisms of MSC on the improvement of osteoporosis is MAPK signal, knocking down phosphorylated JNK (p-JNK) can reverse the proliferation improvement of hFOB 1.19 from MSC-Exo.

Conclusion

Stem cells are a very hot and cutting-edge research area, and they also have significant clinical application potentials. Compared to ethically controversial embryonic stem cells, MSCs, as one type of the adult stem cells, are more accessible and have become more common in clinical and laboratory studies. As stem cells that support the maintenance of tissue and organ structure, MSCs are also of great research significance.

Where to get Bone Marrow Mesenchymal Stem Cells for research?

AcceGen supplies plenty and the most authentic Bone Marrow Derived Mesenchymal Stem Cells, including Human Bone Marrow Derived Mesenchymal Stem Cell, GFP-Expressing Human Bone Marrow-Derived Mesenchymal Stem Cell, RFP-Expressing Human Bone Marrow-Derived Mesenchymal Stem Cell, as well as Monkey Bone Marrow-Derived Mesenchymal Stem Cell, Feline Mesenchymal Stem Cell, Hamster Bone Marrow Mesenchymal Stem Cell, Canine Bone Marrow Mesenchymal Stem Cell. We also provide Bone Marrow Mesenchymal Stem Cell from different donors, such as Human Bone Marrow Derived Mesenchymal Stem Cell/ Muscular Dystrophy Patient, Human Bone Marrow Derived Mesenchymal Stem Cell/ Type II Diabetes Patient, Human Bone Marrow Derived Mesenchymal Stem Cell/ Amyotrophic Lateral Sclerosis Patient and so on. Whatever you need, you can find it here in AcceGen.

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.

References

1. Atala A LR: Handbook of Stem Cells. Academic Press; 2012-12-31.

2. Becker AJ, Mc CE, Till JE: Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963, 197:452-454.

3. Siminovitch L, McCulloch EA, Till JE: THE DISTRIBUTION OF COLONY-FORMING CELLS AMONG SPLEEN COLONIES. J Cell Comp Physiol 1963, 62:327-336.

4. Cong YS, Wright WE, Shay JW: Human telomerase and its regulation. Microbiol Mol Biol Rev 2002, 66:407-425, table of contents.

5. He S, Nakada D, Morrison SJ: Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol 2009, 25:377-406.

6. HR S: The Potential of Stem Cells: An Inventory. Ashgate Publishing; 2007.

7. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. Science 1998, 282:1145-1147.

8. Nolan A: “What is a stem cell”. anthonynolanorg 17 February 2022.

9. Takahashi K, Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126:663-676.

10. Bethesda M: Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation. National Institutes of Health, US Department of Health and Human Services 2010.

11.Lo B, Parham L: Ethical issues in stem cell research. Endocr Rev 2009, 30:204-213.

12. Tonk CH, Witzler M, Schulze M, Tobiasch E: Mesenchymal Stem Cells. In Essential Current Concepts in Stem Cell Biology. Edited by Brand-Saberi B. Cham: Springer International Publishing; 2020: 21-39

13. Ankrum JA, Ong JF, Karp JM: Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol 2014, 32:252-260.

14. Caplan AI: Mesenchymal Stem Cells: Time to Change the Name! Stem Cells Transl Med 2017, 6:1445-1451.

15. Mahla RS: Stem Cells Applications in Regenerative Medicine and Disease Therapeutics. Int J Cell Biol 2016, 2016:6940283.

16. Phinney DG, Prockop DJ: Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair–current views. Stem Cells 2007, 25:2896-2902.

17. Shi S, Bartold PM, Miura M, Seo BM, Robey PG, Gronthos S: The efficacy of mesenchymal stem cells to regenerate and repair dental structures. Orthod Craniofac Res 2005, 8:191-199.

18. Aggarwal S, Pittenger MF: Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005, 105:1815-1822.

19. Augello A, Tasso R, Negrini SM, Cancedda R, Pennesi G: Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum 2007, 56:1175-1186.

20. Meisel R, Brockers S, Heseler K, Degistirici O, Bülle H, Woite C, Stuhlsatz S, Schwippert W, Jäger M, Sorg R, et al: Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase. Leukemia 2011, 25:648-654.

21. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284:143-147.

22. Mushahary D, Spittler A, Kasper C, Weber V, Charwat V: Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 2018, 93:19-31.

23. Otsuru S, Hofmann TJ, Olson TS, Dominici M, Horwitz EM: Improved isolation and expansion of bone marrow mesenchymal stromal cells using a novel marrow filter device. Cytotherapy 2013, 15:146-153.

24. Soleimani M, Nadri S: A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat Protoc 2009, 4:102-106.

25. Zhao P, Xiao L, Peng J, Qian YQ, Huang CC: Exosomes derived from bone marrow mesenchymal stem cells improve osteoporosis through promoting osteoblast proliferation via MAPK pathway. Eur Rev Med Pharmacol Sci 2018, 22:3962-3970.