Chapter 31 Mesenchymal Stem Cell Therapy Flashcards

1
Q

What are the two broad classifications of stem cells?

A

Embryonic stem cells (ESC) and adult stem cells (ASC).

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2
Q

What is the difference between totipotent and pluripotent stem cells?

A

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.

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3
Q

Where are pluripotent stem cells isolated from?

A

The inner cell mass of the blastocyst.

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4
Q

What is stem cell plasticity?

A

The potential of adult stem cells to differentiate into cell types of tissue lineages different from their tissue of origin.

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5
Q

What are mesenchymal stem cells (MSCs) capable of differentiating into?

A

Fibroblasts, osteoblasts, chondroblasts, adipocytes, and skeletal muscle cells.

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6
Q

What are the potential applications of MSCs in equine medicine?

A

Treatment of orthopedic injuries, ischemic, inflammatory, and neurologic disorders.

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7
Q

How do MSCs contribute to tissue regeneration?

A

By differentiating into various tissue types and secreting immunomodulatory and bioactive trophic factors.

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8
Q

What are the immunomodulatory properties of MSCs?

A

They affect both innate and adaptive immunity through direct cell-cell contact or via soluble factors.

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9
Q

What is the significance of pro-inflammatory cytokines in MSC function?

A

They stimulate MSCs to secrete various immunosuppressive factors.

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10
Q

What are some immunosuppressive factors produced by MSCs?

A

IL-6, PGE2, TGF-beta, IDO, and HGF.

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11
Q

How do MSCs inhibit T cell proliferation?

A

Through factors like PGE2, IDO, TGF-beta, HGF, iNOS, and galectins.

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12
Q

What sources are commonly used to derive equine MSCs?

A

Bone marrow (BM), adipose tissue (AdT), umbilical cord blood (UCB), and peripheral blood (PB).

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13
Q

What are the advantages of using adipose tissue for MSC extraction?

A

Higher cell yield per unit volume and the ability to inject the stromal vascular fraction (SVF) without a cell culture step.

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14
Q

What is a significant advantage of umbilical cord blood as a source of MSCs?

A

It is a non-invasive source and can be collected easily at parturition.

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15
Q

What challenges are associated with peripheral blood-derived MSCs?

A

Varying success rates of MSC isolation, ranging from 40–66%.

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16
Q

What is the role of MSCs in wound repair?

A

They improve healing of skin defects and support tissue regeneration.

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17
Q

What is the significance of the ability of MSCs to adhere to tissue culture plastic?

A

It is a common characteristic used to identify MSCs.

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18
Q

What are some of the potential therapeutic applications of MSCs in equine medicine?

A

Treating tendon injuries, cartilage defects, osteoarthritis, bone regeneration, immune-mediated diseases, ischemic diseases, wound repair, and ophthalmological conditions.

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19
Q

What are the morphological characteristics of MSCs in culture?

A

Spindle-shaped cells that grow in a monolayer with varying cellular morphology.

20
Q

What is the challenge in immunophenotyping equine MSCs?

A

Limited availability of species-specific or cross-reacting antibodies.

21
Q

What is a key feature of MSCs in terms of immunogenicity?

A

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.

22
Q

What are the benefits of using allogeneic MSCs over autologous MSCs?

A

Allogeneic MSCs provide a standardized and readily available product without the lag period associated with autologous MSC isolation and expansion.

23
Q

What is the primary use of MSCs in orthopedic injuries?

A

To repair and regenerate tendon, cartilage, and bone tissues.

24
Q

What is the role of MSCs in treating tendon injuries?

A

They stimulate intrinsic healing, decrease inflammation, reduce scar tissue formation, and lower the re-injury rate.

25
Q

What is the potential of MSCs in treating cartilage defects?

A

They can differentiate into chondrocytes and improve cartilage repair and regeneration.

26
Q

What challenges are associated with using MSCs for cartilage repair?

A

The compressive load on injected cells and scaffolds, and the limited ability to repair diffuse osteoarthritic damage.

27
Q

What is the significance of microfracture in cartilage repair?

A

It stimulates cartilage repair by providing access for chondrogenic progenitor cells and growth factors.

28
Q

What are the challenges of treating osteoarthritis with MSCs?

A

Diffuse damage to cartilage and periarticular tissues, and the need for combined treatment approaches.

29
Q

What is the role of MSCs in bone regeneration?

A

They stimulate the natural processes of bone repair, particularly in cases of substantial bone loss or insufficient healing potential.

30
Q

What are the current limitations of MSC therapy for bone regeneration in horses?

A

Lack of controlled clinical studies and variability in treatment protocols.

31
Q

What is the potential of MSCs in treating immune-mediated and inflammatory diseases?

A

Their immunomodulatory properties make them useful for modulating local inflammatory responses and promoting tissue repair.

32
Q

What are some equine autoimmune diseases where MSC therapy might be relevant?

A

Equine recurrent uveitis and pemphigus foliaceus.

33
Q

What is the potential application of MSCs in ischemic diseases?

A

They can improve treatment outcomes for conditions like laminitis by modulating local ischemic responses.

34
Q

What are the potential benefits of MSCs in wound repair?

A

They enhance healing and integration of grafts in skin defects and other soft tissue injuries.

35
Q

What is the role of MSCs in ophthalmological conditions?

A

They can improve outcomes in chronic cases of corneal ulcers and retinal detachment.

36
Q

What is the potential of MSCs in treating neurological disorders?

A

Their ability to differentiate into neurogenic progenitors and secrete trophic factors supports potential applications in neurodegenerative diseases.

37
Q

What are the primary mechanisms through which MSCs modulate immune responses?

A

Through direct cell-cell contact and the secretion of soluble immunosuppressive factors.

38
Q

What factors influence the immunomodulatory effects of MSCs?

A

The level of inflammation in the microenvironment and the specific cytokines present.

39
Q

What are the potential risks associated with the use of allogeneic MSCs?

A

Storage expenses, the need for additional tests to ensure safety, and potential for immune reactions.

40
Q

What is the significance of conducting well-designed clinical trials for MSC therapy?

A

To ensure the safety, efficacy, and optimal application of MSC treatments in equine medicine.

41
Q

What are some methods used to characterize differentiated equine MSCs?

A

Histological staining, gene expression analysis, and protein expression profiling.

42
Q

What are the benefits of using autologous MSCs in therapy?

A

Reduced risk of immune reactions and no need for extensive compatibility testing.

43
Q

What are some sources of MSCs that are gaining interest due to less invasive collection methods?

A

Umbilical cord blood, peripheral blood, umbilical cord matrix, amnion, tendon, muscle, and periosteal tissue.

44
Q

What is the role of MSCs in regenerative medicine?

A

They support the repair and regeneration of damaged tissues through differentiation and secretion of bioactive factors.

45
Q

What are some key considerations for successful MSC therapy?

A

Accurate determination of the route, timing of injection, cell number administered, and the specific condition being treated.

46
Q

What are the potential applications of MSCs beyond orthopedic injuries?

A

Treating immune-mediated, inflammatory, ischemic, and neurologic disorders, as well as improving wound repair and ophthalmological conditions.