414 Canine Sports Medicine and Rehabilitation
3–6 weeks are used to increase the total number
of MSCs (Crovace et al., 2010) (Figure 16.7).
Adipose tissue can also be used as a source
of MCSs for the culture expansion technique
(Guercio et al., 2012). Several studies have char‑
acterized adipose‐derived MSCs (AD‐MSCs)
and evaluated their ability to differentiate into
chondrogenic, osteogenic, and adipogenic lines
(Neupane et al., 2008; Guercio et al., 2012, 2013).
A recent study compared bone marrow MSCs
(BM‐MSCs) with AD‐MSCs and concluded that
higher isolation success and proliferation rates
were found with adipose tissue (Russell et al.,
2016). In contrast, another study showed that
BM‐MSCs may have greater osteogenic poten‑
tial than AD‐MSCs when obtained from young
dogs (Alves et al., 2014).
Another strategy to isolate MSCs is by enzy‑
matic digestion followed by filtration and
centrifugation of adipose tissue. This process
results in the stromal vascular fraction, a mix‑
ture of cells, which is injected, without cell
culture, into the patient. This approach has the
advantage of providing cells more quickly as
culture is not required so it can be prepared
patient‐side. The benefits of adipose tissue for
cell isolation include more abundant tissue,
accessibility, and potentially higher MSC popu‑
lations. However, only a small percentage of
the cells derived from adipose tissue digestion
are MSC, with a maximum of 7.7% of cells
meeting the most lenient definition of MSCs
(Sullivan et al., 2016). The stromal vascular frac‑
tion has been compared with bone marrow
aspirate for the amount of tissue harvested, the
ease of harvest, and the cellular content in each
sampled tissue. Although the highest cell num‑
ber in average was found in bone marrow, the
adipose stromal vascular fraction yielded
more consistent results, supporting the authors’
conclusion of recommending the falciform
ligament as the first choice for harvest (Sullivan
et al., 2016).Mechanism of actionDespite the large number of experimental stud‑
ies, the mechanism of action of MSCs is still
unclear. MSCs are identified by specific proper‑
ties that relate to their potential therapeutic
action. MSCs have demonstrated the ability to
migrate to sites of injury and inflammation
(Maerz et al., 2017). The tissue trauma induces
increased expression of inflammatory cytokines
and chemokines and initiates the mobilization of
marrow‐derived cells. MSCs migrate to injured
tissue to participate in regenerative and/or
immunomodulatory pathways. The original
hypothesis was that MSCs would regenerate tis‑
sue based on the ability of the MSCs to differen‑
tiate into the host tissue. Meniscus regeneration
is often used as an example for a MSC‐based
treatment aiming at tissue regeneration (Horie
et al., 2012). Limited results from animal studies
would suggest a potential for using intra‐articu‑
lar injection of MSCs for the regeneration of
meniscus. However, it should be considered that
spontaneous meniscal regeneration has been
observed following meniscectomy.
A recent paradigm shift has emerged suggest‑
ing that MSCs may act on the local environment(A) (B) (C) (D)Figure 16.7 Maturation during culture of bone marrow‐derived mesenchymal stem cells including: (A) cells on the day
of culture, (B) after several days of culture, (C) after 10–14 days of culture, and (D) at 4 weeks of culture.