Chapter 31 Mesenchymal Stem Cell Therapy Flashcards
What are the two broad classifications of stem cells?
Embryonic stem cells (ESC) and adult stem cells (ASC).
What is the difference between totipotent and pluripotent stem cells?
Totipotent stem cells can form all cell types including extra-embryonic tissues, while pluripotent stem cells can form all cell types except extra-embryonic tissues.
Where are pluripotent stem cells isolated from?
The inner cell mass of the blastocyst.
What is stem cell plasticity?
The potential of adult stem cells to differentiate into cell types of tissue lineages different from their tissue of origin.
What are mesenchymal stem cells (MSCs) capable of differentiating into?
Fibroblasts, osteoblasts, chondroblasts, adipocytes, and skeletal muscle cells.
What are the potential applications of MSCs in equine medicine?
Treatment of orthopedic injuries, ischemic, inflammatory, and neurologic disorders.
How do MSCs contribute to tissue regeneration?
By differentiating into various tissue types and secreting immunomodulatory and bioactive trophic factors.
What are the immunomodulatory properties of MSCs?
They affect both innate and adaptive immunity through direct cell-cell contact or via soluble factors.
What is the significance of pro-inflammatory cytokines in MSC function?
They stimulate MSCs to secrete various immunosuppressive factors.
What are some immunosuppressive factors produced by MSCs?
IL-6, PGE2, TGF-beta, IDO, and HGF.
How do MSCs inhibit T cell proliferation?
Through factors like PGE2, IDO, TGF-beta, HGF, iNOS, and galectins.
What sources are commonly used to derive equine MSCs?
Bone marrow (BM), adipose tissue (AdT), umbilical cord blood (UCB), and peripheral blood (PB).
What are the advantages of using adipose tissue for MSC extraction?
Higher cell yield per unit volume and the ability to inject the stromal vascular fraction (SVF) without a cell culture step.
What is a significant advantage of umbilical cord blood as a source of MSCs?
It is a non-invasive source and can be collected easily at parturition.
What challenges are associated with peripheral blood-derived MSCs?
Varying success rates of MSC isolation, ranging from 40–66%.
What is the role of MSCs in wound repair?
They improve healing of skin defects and support tissue regeneration.
What is the significance of the ability of MSCs to adhere to tissue culture plastic?
It is a common characteristic used to identify MSCs.
What are some of the potential therapeutic applications of MSCs in equine medicine?
Treating tendon injuries, cartilage defects, osteoarthritis, bone regeneration, immune-mediated diseases, ischemic diseases, wound repair, and ophthalmological conditions.
What are the morphological characteristics of MSCs in culture?
Spindle-shaped cells that grow in a monolayer with varying cellular morphology.
What is the challenge in immunophenotyping equine MSCs?
Limited availability of species-specific or cross-reacting antibodies.
What is a key feature of MSCs in terms of immunogenicity?
They are considered minimally or non-immunogenic due to low expression of MHC class I and lack of MHC class II and co-stimulatory molecules.
What are the benefits of using allogeneic MSCs over autologous MSCs?
Allogeneic MSCs provide a standardized and readily available product without the lag period associated with autologous MSC isolation and expansion.
What is the primary use of MSCs in orthopedic injuries?
To repair and regenerate tendon, cartilage, and bone tissues.
What is the role of MSCs in treating tendon injuries?
They stimulate intrinsic healing, decrease inflammation, reduce scar tissue formation, and lower the re-injury rate.
What is the potential of MSCs in treating cartilage defects?
They can differentiate into chondrocytes and improve cartilage repair and regeneration.
What challenges are associated with using MSCs for cartilage repair?
The compressive load on injected cells and scaffolds, and the limited ability to repair diffuse osteoarthritic damage.
What is the significance of microfracture in cartilage repair?
It stimulates cartilage repair by providing access for chondrogenic progenitor cells and growth factors.
What are the challenges of treating osteoarthritis with MSCs?
Diffuse damage to cartilage and periarticular tissues, and the need for combined treatment approaches.
What is the role of MSCs in bone regeneration?
They stimulate the natural processes of bone repair, particularly in cases of substantial bone loss or insufficient healing potential.
What are the current limitations of MSC therapy for bone regeneration in horses?
Lack of controlled clinical studies and variability in treatment protocols.
What is the potential of MSCs in treating immune-mediated and inflammatory diseases?
Their immunomodulatory properties make them useful for modulating local inflammatory responses and promoting tissue repair.
What are some equine autoimmune diseases where MSC therapy might be relevant?
Equine recurrent uveitis and pemphigus foliaceus.
What is the potential application of MSCs in ischemic diseases?
They can improve treatment outcomes for conditions like laminitis by modulating local ischemic responses.
What are the potential benefits of MSCs in wound repair?
They enhance healing and integration of grafts in skin defects and other soft tissue injuries.
What is the role of MSCs in ophthalmological conditions?
They can improve outcomes in chronic cases of corneal ulcers and retinal detachment.
What is the potential of MSCs in treating neurological disorders?
Their ability to differentiate into neurogenic progenitors and secrete trophic factors supports potential applications in neurodegenerative diseases.
What are the primary mechanisms through which MSCs modulate immune responses?
Through direct cell-cell contact and the secretion of soluble immunosuppressive factors.
What factors influence the immunomodulatory effects of MSCs?
The level of inflammation in the microenvironment and the specific cytokines present.
What are the potential risks associated with the use of allogeneic MSCs?
Storage expenses, the need for additional tests to ensure safety, and potential for immune reactions.
What is the significance of conducting well-designed clinical trials for MSC therapy?
To ensure the safety, efficacy, and optimal application of MSC treatments in equine medicine.
What are some methods used to characterize differentiated equine MSCs?
Histological staining, gene expression analysis, and protein expression profiling.
What are the benefits of using autologous MSCs in therapy?
Reduced risk of immune reactions and no need for extensive compatibility testing.
What are some sources of MSCs that are gaining interest due to less invasive collection methods?
Umbilical cord blood, peripheral blood, umbilical cord matrix, amnion, tendon, muscle, and periosteal tissue.
What is the role of MSCs in regenerative medicine?
They support the repair and regeneration of damaged tissues through differentiation and secretion of bioactive factors.
What are some key considerations for successful MSC therapy?
Accurate determination of the route, timing of injection, cell number administered, and the specific condition being treated.
What are the potential applications of MSCs beyond orthopedic injuries?
Treating immune-mediated, inflammatory, ischemic, and neurologic disorders, as well as improving wound repair and ophthalmological conditions.
