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MSCS FOR CHRONIC WOUND TREATMENTS 563

primarily on the etiology of the disease, showing some frustrating and time-consuming. Considering that MSCs pos-
variations among diabetic foot ulcers, venous leg ulcers, and sess the ability to promote skin wound healing, several clinical
peripheral arterial occlusive ulcers. Interestingly, even in the studies have been performed to determine the therapeutic po-
treatment of the same disease, the inclusion/exclusion cri- tential of MSCs for pressure sores (Table 4).
teria are inconsistent among different studies, which would In 2008, Yoshikawa et al. treated 11 patients suffering from
hamper a good comparison among these treatments. There- pressure sores that had persisted for more than 3 months with
fore, consistent inclusion/exclusion criteria are needed in the autologous cultured marrow mesenchymal cells impregnated
future. on a collagen sponge. 158 In 9 of the 11 patients, the ulcer
Despite the inconsistency mentioned above, it is noted almost healed; in the remaining 2 patients, the ulcers became
that there are several exclusion criteria that are generally smaller in size after treatment, but the patients died for reasons
considered during the selection of patients: (i) pregnant or unrelated to grafting (heart failure and renal failure, respec-
nursing females; (ii) active infection of the wound and tively). Long-term follow-up of those surviving patients was
surrounding tissue; (iii) active malignancy or a history of favorable: except for two patients with worsened nutritional
malignancy within the last 5 years (except for basal cell state, the decubitus ulcers in the other seven patients did not
carcinoma in situ); (iv) systemic bacterial or viral infection recur for at least 1-year posttreatment.
(hepatitis B virus, hepatitis C virus, human immunodefi- In another study, Sarasu ´a et al. assessed the utility of
ciency virus, and so on); (v) severe heart, liver, kidney, or autologous bone marrow mononuclear cells, which contain
lung function failure; (vi) a psychiatric condition or chronic MSCs and other stem/progenitor cells, for the treatment of
alcohol or drug abuse problem; and (vii) participation in any pressure ulcers in patients with spinal cord injury. 159
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other clinical study that would interfere with the study. Twenty-two patients with single type IV pressure ulcers
were recruited. After treatment, the pressure ulcers healed in
Radiation burns 19 patients, and none of the healed ulcers recurred within a
mean follow-up period of 19 months.
Severe radiation burns continue to be a significant chal-
According to the clinical trials (Table 3) and the clinical
lenge in advanced wound care, because they are often re-
study in the literature (Table 4), the inclusion/exclusion
sistant to conventional treatments or advanced surgery (e.g.,
criteria of these researches were inconsistent, indicating a
flap coverage and skin grafting). The management of severe
21 need for further investigations to better define the standards
radiation burns is very lengthy and difficult. Therefore,
for patient selection.
several studies have explored the therapeutic potential of
stem/progenitor cells for radiation burns.
Lataillade et al. first treated severe radiation burns with Challenges and Outlook
autologous cultured BM-MSCs. One month after treatment, Many challenges need to be addressed before MSCs
the wounds healed almost completely, without recurrence of fulfill their therapeutic potential for chronic wounds, espe-
radiation inflammatory waves in the following 11 months. 154 cially the choice of seed cells, the safety of cells, and the
In 2010, Bey et al. reported another successful treatment of a treatment method.
severe radiation burn through a combination of local injec-
tion of autologous BM-MSCs and skin autograft. The clini- The sources of MSCs
cal outcome was favorable and the radiation inflammatory
waves did not reoccur in the 8-month follow-up period. 155 There are considerable differences in the biological prop-
Besides autologous BM-MSCs, allogenic BM-MSCs de- erties of MSCs derived from different tissues, ranging from
43–45
rived from cadaveric donor have been used to treat a radiation differentiation potential to immunomodulatory ability.
burn, which had failed to positively respond to conventional Thus, tissue origin is an important consideration in MSC-
treatments for more than 30 years. 156 In this case, cadaveric based therapy. Although both adult and perinatal tissues have
BM-MSCs suppressed successive inflammatory waves and been used in clinical trials, it remains unclear which one is the
improved the healing of impaired tissues, including improved optimal source of MSCs for widespread clinical applications;
vasculature and skin quality. therefore, future studies are recommended to determine the
Although these case studies are encouraging (Table 4), the influence of tissue origin of MSCs on their wound-healing
strength of their findings is limited by the small number of potential.
patients involved, a combination of different treatment mo- MSCs contain various subpopulations. Although the
dalities, and the absence of controls. In addition, there is still a wound-healing potential of MSCs as a pool of heteroge-
striking lack of inclusion/exclusion criteria for MSC-based neous cell populations has shown to be very promising, the
therapy for radiation burns. Obviously, more studies are needed role of specific cell subpopulations and their individual
to validate the safety and efficiency of MSCs for radiation wound-healing potentials remain unknown. Identifying
burns. Also, if the therapy is confirmed to be safe and efficient which cell population possesses the most beneficial thera-
enough, establishing detailed standards for patient selection is peutic effect will provide valuable information for the
still required before wide clinical applications. quality control of MSCs for clinical applications, which
guarantee a reproducible repair outcome.
Pressure sores
The safety of MSCs
Pressure sores are a significant cause of morbidity, resulting
from unrelieved pressure against skin. Although many pre- Administration of MSCs is not without risk, which should
ventative and treatment modalities have been developed in not be neglected when developing clinical protocols. Several
recent years, 20,157 the treatment of pressure ulcers remains key points should be considered, including the malignant