Front Matter

Chapter 16 Biological Therapies in Canine Sports Medicine 413

Stem cells

Definitions and sources

The use of MSC therapies in veterinary patients
is a field that is evolving rapidly, both experimen‑
tally and clinically. MSCs have received increas‑
ing attention due to the potential of augmenting
healing of muscles, tendons, ligaments, and
bone. However, the lack of strict regulations has
led to the proliferation of commercially available
products and therapies that have either not been
tested or have not demonstrated efficacy. Many
questions remain unanswered, including the best
tissue source, best method of collection and prep‑
aration, ideal cell numbers, and best administra‑
tion technique. A summary of the sources of
various stem cell types, and their effects, clinical
uses, and limitations is provided in Table 16.1.
Stem cells are defined based on their ability to
differentiate into a wide range of cells and to self‐
renew. Stem cells can be classified in different
ways, although the classification based on the
source may be the most relevant for the clinician.
Embryonic stem cells are derived from embryos
at a developmental stage; induced pluripotent
cells are engineered by manipulating the expres‑
sion of certain genes; adult stem cells, applicable
to clinical uses, are undifferentiated multipotent
cells, found throughout the body after embryonic
development. Their function is to repair tissue
and replenish senescent cells. Among the adult
stem cells, MSCs have the important advantage of

being more readily available and easy to obtain

compared with embryonic and fetal stem cells.

Sources of MSCs include fetal tissue such as

umbilical cord, and blood and adult tissues such

as bone marrow, skin, adipose tissue, synovium,

periosteum, and dental pulp. Because tumor for‑

mation has been reported after application of

embryonic stem cells, potential adverse effects

include stem cell‐induced carcinogenesis and tis‑

sue formation. However, multipotent MSCs used

in most studies are in a more committed cell stage

and have far more limited differentiation poten‑

tial than totipotent embryonic stem cells. As a

result, there is no published evidence demonstrat‑

ing carcinogenesis of multipotent MSC in either

in vitro or in vivo models (Hernigou et al., 2013).

MSCs are undifferentiated cells that have

unique characteristics as they can (1) move dur‑

ing angiogenesis; (2) differentiate into special‑

ized cell types (e.g., chondrocyte, osteocyte); (3)

proliferate and regenerate; and (4) release

immune regulators and growth factors. More

specifically, MSCs are defined based on their

ability to differentiate in  vitro into osteoblasts,

adipocytes, or chondroblasts, adhere to plastic,

and express specific genes. The first application

of MSC‐based therapy in veterinary medicine

was performed in horses using bone marrow

aspirate for treating suspensory ligament

desmitis. Bone marrow is an attractive source

for MSCs, although only a very small cellular

fraction corresponds to MSCs (<0.001%). For

this reason, culture expansion techniques over

Table 16.1 Comparison of stem cells from different sources: their effects, uses, and limitations

Hematopoietic stem cells Embryonic stem cells Mesenchymal (adult) stem cells

Source Bone marrow

(autologous or allogeneic)

Blastocysts/early embryo

(allogeneic)

Bone marrow, fat, cord blood

(autologous or allogeneic)

Potency Multipotent Pluripotent Multilineage differentiation

Beneficial

effects

Transplantation of healthy cells in

diseased individual

Source of biological

material for various cell

restorative treatments

Anti‐inflammatory; anti‐apoptotic;

differentiation into cartilage,

muscle, bone, nerve cells

Clinical

uses

Neoplastic disorders of blood and bone

marrow; autoimmune disease; skeletal

dysplasia; mucopolysaccharidosis

Potential for tissue

regeneration

Regeneration of several

tissues, e.g., tendons, neurons,

chondrocytes, cornea

Limitations Potential for graft versus host reaction Risk for tumor formation

Ethical concerns

Legal restrictions

Difficult to identify, isolate,

maintain, and culture