Page 37 - Exosomes - wound healing power

Dovepress Clinical use of mesenchymal stem cells in meniscal repair

In 2014, a randomized, double-blind, placebo-controlled minimally invasive, nonsurgical alternative, many issues
study involving 55 patients, who underwent a partial menis- (challenges and limitations) need to be resolved. First, more
cectomy (resection of at least 50%), was conducted. Patients human studies are required, using a variety of different
were randomly assigned to receive allogeneic, culture- sources of MSCs and applying them to different categories
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expanded, bone marrow-derived stem cells. Patients were of meniscal tears.
randomized into one of three treatment groups: Group A, Second, the mechanism of how MSCs may repair menis-
in which patients received an intra-articular injection of cal tears is unclear. Some of the possible mechanisms are:
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50×10 allogeneic MSCs; Group B, who received 150×10 1) secretory and trophic effects of the stem cells injected 35,36 ;
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allogeneic MSCs; and the control group, who received 2) direct engraftment and differentiation of the stem cells
sodium hyaluronate as a placebo. The patients who received introduced into the joints 37,38 ; or 3) the combination of
MSCs showed clinical improvement, assessed with the VAS mechanisms (1) and (2). MSCs secrete a variety of cytokines,
and self-Lysholm knee scale, and also showed significant chemokines, growth factors, and exosomes. 39,40 These fac-
meniscal volume regeneration, seen on MRI at 1 year tors have positive effects on the growth of the surrounding
postimplantation. 16 progenitor cells. Furthermore, some evidence exists that the
In 2014, Pak et al reported a case study in which a percu- injected stem cells may actually become engrafted into the
taneous intra-articular injection of autologous ASCs, in the tissue and differentiate into tissue-specific cells. 41
form of SVF, along with PRP, hyaluronic acid, and CaCl , Third, the fate of MSCs injected into a joint needs to be
2
repaired a meniscal tear in a 32-year-old female by regen- further elucidated. According to a preclinical study, knee-
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For personal use only. Open Access Journal of Sports Medicine downloaded from https://www.dovepress.com/ by 68.175.65.102 on 25-Mar-2017 SVF was obtained by processing autologous lipoaspirates However, the ultimate fate of MSCs injected into a joint is
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erating a meniscal cartilage. Again, the ASCs-containing
injected MSCs stays only in the knee joint after the injection.
not yet clear in clinical studies. MSCs may stay in the joint,
with collagenase. The mixture (ASCs-containing SVF with
attached to the lesion, and may become integrated into the
PRP, hyaluronic acid, and CaCl ) was then injected into the
2
medial tibiofemoral joint of the patient on the same day the
SVF was obtained. The patients received four additional target tissue, prolonging their own survival. However, some
of the MSCs that are not integrated into the tissue may be
doses of PRP with CaCl and hyaluronic acid on days 3, 7, removed slowly while secreting various trophic factors.
2
14, and 28. Afterward, a near-complete repair of the torn Lastly, properly designed clinical studies with valid
meniscus was seen on a repeat MRI performed at 3 months control treatments (eg, saline) may be necessary to make
postimplantation. 19 an accurate conclusion regarding the effect of MSCs in
In 2016, a single-center, prospective, open-label study regenerating meniscal cartilage. Currently, there are studies
involving five patients with an avascular meniscal tear was comparing PRP to MSCs to confirm the regenerative effects
conducted. Autologous MSCs were isolated from an iliac of MSCs. 43,44 However, it is also necessary to include saline
34
crest bone marrow biopsy, expanded, and seeded into the col- or other inert placebo therapy in a control group to establish
lagen scaffold. The resulting human MSC/collagen-scaffold the real regenerative effects of MSCs.
implant was placed into the meniscal tear of five patients. The
patients were followed for 24 months. All five patients treated Conclusion
showed significant clinical improvement on repeated mea- A comprehensive review of the literature suggests that MSCs
sures analysis (Tegner–Lysholm score, range of motion, and possess an intrinsic therapeutic potential that can directly and
the International Knee Documentation Committee [IKDC] indirectly contribute to cartilage regeneration, thus poten-
score). Three of the five patients were asymptomatic at 24 tially healing meniscal tears and offering great potential as
months with clinical improvement in knee function scores an alternative treatment modality. The meniscal tissue is a
and without any evidence of recurrent meniscal tear on MRI crucial structure that functions to provide knee stability, shock
studies. Two patients required subsequent meniscectomy due absorption, and nutrition to articular cartilages. However,
to retear or nonhealing of the meniscal tear at ~15 months once the knee is injured, the current treatment modality of
after implantation. No other adverse events occurred. 34 meniscectomy may lead to an early development of OA in
the treated knee. Thus, new treatment strategies are neces-
Discussion sary to regenerate the damaged tissue without causing such
Currently, only a few successful applications of MSCs in detrimental side effects. Regenerative medicine using MSCs
repairing human meniscal tears have been documented. Thus, may offer an alternative strategy that does not result in an
before general application of this potentially promising, early development of OA in the treated knee.

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