Lopes L. Stem Cell Res Ther. 2018 Jul 11;9(1):188.

Lopes L. et al., conducted a study which reviewed current literature which reported stem cell therapy for DFU, in priority to the type and origin of the stem cells used for treatment, routes of cell administration, use of granulocyte-colony stimulating factor (G-CSF), and adjunctive use and comparison to percutaneous transluminal angioplasty. The search for databases was done on PubMed, EMBASE, and Google Scholar. MeSH terms were used for search on “diabetic foot” paired with MeSH terms for “stem cell(s)” or “progenitor cells”, which resulted in 256 articles available for screening. Screening and review of abstracts for all these articles were done, including experimental research articles describing stem cell therapy for diabetic foot ulcers. Initially 256 articles were screened out of which 58 studies were selected, consisting of 45 primary research studies and 13 reviews, which were reviewed in depth. A secondary screening was performed on 13 reviews, yielding an additional 54 primary research studies which made 99 primary research studies excluding an additional full text review 10 articles, leading to the final 89 primary research articles. 89 research papers were examined in detail to determine study design (preclinical or clinical).

Results observed were:

Study design

  • From 89 selected articles, 54 were preclinical studies (60.7%) and 36 were clinical studies (40.4%)

Clinical studies

  • One clinical study was retrospective and 35 studies were prospective

Stem cell type

Adult stem cells

  • The most frequently used cell type in both preclinical and clinical studies was Bone marrow-derived mesenchymal stem cells (BM-MSC)
  • In 11 preclinical studies and 3 clinical studies adipose-derived stem cells (ADSC) were used.
  • In 12 preclinical and 4 clinical studies human umbilical cord-derived mesenchymal stem cells (hUC-MSC) were used
  • The second most frequent cell type in clinical studies was peripheral blood-derived mesenchymal stem cells (PB-MSC) used in 2 preclinical studies

Granulocyte-colony stimulating factor (G-CSF)

  • The optimal G-SCF administration protocols were 5 μg/kg/day for 5 days or 10 μg/kg/day for 4 days to activate patients with a DFU who received PB-MSC

Stem cell origin

  • In preclinical studies, allogeneic stem cells were used in the majority and only four (7%) examined autologous stem cells
  • In clinical studies autologous stem cells were used by 32 (89%), and only four (11%) used allogeneic cells

Administration route

Local administration

  • The most commonly used route of administration was Nonvascular injections to directly treat a DFU in 28 preclinical studies (52%) and 31 clinical studies (86%)
  • In preclinical studies Intradermal (n = 11) and subcutaneous (n = 8) injections were more frequently used while in clinical studies the intramuscular (n = 24) route was more commonly used
  • Topical administration was also generally done in 23 preclinical studies (43%) and five clinical studies (14%).

Systemic administration

  • Endovascular stem cell delivery was done in five preclinical (9%) and six clinical (17%) studies

Stem cell therapy and angioplasty

  • Cell therapy was correlated with superior wound healing despite similar TcPO2 and amputation-free survival in comparison with angioplasty

 

Thus, it concluded that stem cell therapy is an effective treatment for diabetic foot ulcers and is currently used as an alternative to amputation for some patients without other options for revascularization.