Mesenchymal Stem Cell FAQs

Mesenchymal stem cells (MSCs) are defined as a self-renewing population of adherent multipotent progenitor cells with the capacity to differentiate into several mesenchymal cell lineages including bone, cartilage and adipose tissue. Recently, mesenchymal stem cells have become cells of increased interest due to their use in potential allogenic stem cell therapies.

What are mesenchymal stem cells?

Mesenchymal stem cells (MSCs) are multipotent adult stem cells, which can self-renew by dividing and can differentiate into various tissues including, bone, cartilage, adipose tissue (fat cells), connective tissue and muscle.¹

What are the types of mesenchymal stem cells?

Mesenchymal stem cells are categorized based on the origin, such as bone marrow-derived MSCs (BM-MSCs), umbilical cord MSCs, adipose-derived MSCs (ASCs), heart MSCs and lung MSCs.²

Where do mesenchymal stem cells come from?

They are majorly isolated from bone marrow. However, cells which display characteristics of mesenchymal stem cells are also found in adipose tissue, peripheral blood, cord blood, skin, cartilage, synovial fluid, bone, tendons, muscle, salivary gland, dental tissues, fetal membrane, endometrium, Wharton’s jelly and sub-amniotic umbilical cord lining membrane.³

What can mesenchymal stem cells differentiate into?

Mesenchymal stem cells differentiate into cells derived from all three lineages, such as:

• Skin, neurons, glial cells derived from ectoderm
• Bone, cartilage, fat and muscle cells derived from mesoderm
• Hepatocytes, pancreatic cells derived from endoderm

What are the methods used to isolate mesenchymal stem cells?

Human mesenchymal stem cells are isolated based on their tissue origin. Majorly, two methods are being used:

• Ficoll density gradient method: Used to isolate mesenchymal stem cells from bone marrow, peripheral blood and synovial fluid.⁴
• Collagenase digestion method: Used to isolate mesenchymal stem cells from adipose, dental, foreskin, endometrium, Wharton’s Jelly and placenta.⁵

What are the characteristics of MSC?

International Society of Cellular therapy has listed specific characteristics of mesenchymal stem cells, which are:⁶

• Adherence to plastic surface
• Expression of cell surface markers, including CD105, CD73 and CD90
• And lack expression of CD45, CD34, CD14 or CD11b, CD79, or CD19 and human leucocyte antigen-DR (HLA-DR)

Which media is used to expand mesenchymal stem cells in culture?

Optimized and high quality MSC expansion media are available including Human Mesenchymal-LS Expansion Medium, Human Mesenchymal-XF Expansion and cGMP compliant Stemline^® Mesenchymal Stem Cell Expansion Medium.

In addition PLTMax^® Human Platelet Lysate is a growth factor rich human derived media supplement that is a superior alternative to fetal bovine serum (FBS) for human mesenchymal stem cell (MSC) culture.

Which media is suitable to differentiate MSC into osteocytes?

OsteoMAX-XF™ is a specially formulated xeno-free media to readily differentiate human mesenchymal stem cells into osteocytes. OsteoMAX-XF was based on patented, bead-based combinatorial technology, that produces mature osteocytes expressing bone-specific and mineralization markers in as little as 7-10 days.

Are there any clinical treatments available using MSC?

No, still they are in clinical trials. The multi-lineage potential and homing ability of MSC offers therapeutic strategies to treat skeletal and neurodegenerative diseases. Considering the secretion of anti-inflammatory molecules and immunoregulatory effects, MSCs are also promising to treat autoimmune and inflammatory diseases.

What are autologous and allogenic MSC and what are its pros and cons?

	Autologous MSC	Allogeneic MSC
Definition	MSC isolated from patient’s own  body and transplanted back into  the patient	MSC isolated from healthy patient and administered into patient
Pros	No objection from FDA to use autologous stem cells for therapeutic application	Stem cells have maximum potency, as they are frequently isolated from younger donors Readily available and can be translated immediately Cost and time effective
Cons	Less potent Difficult to obtain stem cells from elderly patients Systemic diseases alter the intrinsic properties of MSCs	In a long-term, allogeneic MSC could be cleared by host antibodies from the body

Why do mesenchymal stem cells show immunosuppression and low immunogenicity?

Mesenchymal stem cells avoid immune response by:

• Expressing low levels of class I MHC molecules and not expressing class II MHC and co-stimulatory molecules (CD80, CD86 and CD40).
  
• Inhibiting immunogenic activity of T cells, B cell, dendritic cells and natural killer cells either through cell-cell contacts or soluble factors.⁷

Figure 1. The multi-lineage differentiation potential of mesenchymal stem cells. MSC cultures have the multi-lineage capacity to differentiate towards a variety of cell types. Given the ability of MSCs to give rise to a number of cell types, these cells are highly attractive models for investigation, especially in regenerative medicine applications.

References

1. Horwitz E, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini F, Deans R, Krause D, Keating A. 2005. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 7(5):393-395. https://doi.org/10.1080/14653240500319234

2. Hass R, Kasper C, Böhm S, Jacobs R. 2011. Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 9(1): https://doi.org/10.1186/1478-811x-9-12

3. Ullah I, Subbarao R, Rho G. 2015. Human mesenchymal stem cells - current trends and future prospective. 35(2): https://doi.org/10.1042/bsr20150025

4. Raynaud CM, Maleki M, Lis R, Ahmed B, Al-Azwani I, Malek J, Safadi FF, Rafii A. 2012. Comprehensive Characterization of Mesenchymal Stem Cells from Human Placenta and Fetal Membrane and Their Response to Osteoactivin Stimulation. Stem Cells International. 20121-13. https://doi.org/10.1155/2012/658356

5. Schüring AN, Schulte N, Kelsch R, Röpke A, Kiesel L, Götte M. 2011. Characterization of endometrial mesenchymal stem-like cells obtained by endometrial biopsy during routine diagnostics. Fertility and Sterility. 95(1):423-426. https://doi.org/10.1016/j.fertnstert.2010.08.035

6. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E. 2006. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 8(4):315-317. https://doi.org/10.1080/14653240600855905

7. Zhang J, Huang X, Wang H, Liu X, Zhang T, Wang Y, Hu D. 2015. The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy. Stem Cell Res Ther. 6(1): https://doi.org/10.1186/s13287-015-0240-9