As a source of haematopoietic stem cells for transplantation, there are several advantages of using umbilical cord blood stem cells over bone marrow stem cells, another major source of haematopoietic stem cells [17] . Amongst these advantages, there is the fact that umbilical cord blood contains more stem cells per unit of volume than bone marrow. Umbilical cord stem cells are also more tolerant of Human Leukocyte Antigen (HLA) mismatches than those derived from the bone marrow, leading to a lower rate of graft-versus-host disease being observed when umbilical cord stem cells are used for transplantation [18] .

Another major advantage in using umbilical cord stem cells over bone marrow is the ease of collection. Their collection process is not painful to neither the mother nor the child and can be carried out either before or after placental expulsion [19] [20] [21] . An average of 120 mL of blood can be collected with no risk to either the mother or the baby [22] . On the other hand, collection of bone marrow stem cell requires hospitalisation and anesthetisation of the donor. Furthermore, the donor will usually experience post-collection pain and discomfort [13] . The extraction of stem cells from the bone marrow also becomes increasingly difficult with aging as the red marrow space changes to a yellow-marrow as it becomes fat-filled with age [23] .

Umbilical cord blood stem cells also have the capability to be stored in a bank, allowing for their “off-the-shelf” use, unlike bone marrow [23] .

A further advantage of using umbilical cord blood stem cells is the decreased transmission risk of infectious diseases, particularly Epstein-Barr virus and cytomegalovirus as the umbilical cord blood is almost never contaminated by the afore mentioned viruses [20] .

Of interest to note is that adipocyte stem cells are another group of stem cells which have been receiving attention lately due to the substantially large amounts that can be harvested from adipose tissue fragments, and their ease of collection via needle biopsy or liposuction aspirates [24] [25] . Furthermore, adipocyte stem cells are considered to be immunoprivileged, meaning graft-versus-host disease can be prevented when using these stem cells, similar to umbilical cord stem cells [26] [27] .

The first successful umbilical cord blood stem cell transplant was reported as occurring in 1988 as Gluckman and his colleagues showed that the umbilical cord blood (UCB) contained sufficient HSCs for successful haematological reconstitution [28] . The recipient was a 6-year-old American boy from North Carolina who was treated for Fanconi’s anaemia (a genetic disorder) at Hospital St. Louis in Paris, France, using cord blood obtained from his younger sister’s birth [29] . This was followed one year later by the first related umbilical cord blood transplant in the United States [30] .

Kurtzberg et al. are credited with performing the first successful unrelated umbilical cord blood transplant in the United States in 1994 [31] .

Four patients, one male and three females, aged between 26 and 54 years received intravenous infusion of umbilical cord-derived mesenchymal stem cells to treat their condition of chronic refractory immune thrombocytopenia purpura [32] .

This condition is an auto-immune acquired disorder characterised by an accelerated destruction of platelets and an inhibited production of platelets [33] .

The patients were intravenously infused with 10 mL of human umbilical cord-mesenchymal stem cells (hUC-MSCs) at a density of between 5 × 10⁶ and 1 × 10⁷ cells/ml. Responses to the transplant were achieved in all the four patients at the end of the second week after the transplantation. The patients achieved a count of >50 × 10⁹ platelet/L, with 2 patients achieving a count of more than 90 × 10⁹ platelet/L [32] .

One of the patients sustained response after a single transfusion without the need of any further therapy during the follow up. The other three patients had a relapse within 1 year after their first transfusion, but responded well to the second transfusion [32] .

During the entire study period, no clinically significant side effects were reported, with neither ectopic tissue formation nor other illnesses related to the hUC-MSCs treatments being observed [32] .

To conclude, although the data obtained is suggestive of incomplete symptom alleviation, and that the underlying mechanisms of such therapy on ITP need further exploration, this study has managed to show that hUC-MSC transplantation is safe and effective for treating ITP, with an annual optimal period of transplantation [32] .

In this case study, Mallhi et al. present two cases of paediatric germ-line GATA2 mutations presenting with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with monosomy 7.

The first patient was a 16-year-old Caucasian male who received a double umbilical cord blood-hematopoietic stem cell transplantation (UCB-HSCT), while the second patient was an 11-year-old Caucasian male who received a single UCB-HSCT. Both patients were successfully treated, with only limited GVHD being seen in both cases, which responded well to immunosuppressive treatment. At the time of the paper’s publication, there was no evidence of chronic GVHD [34] .

A 56-year-old Chinese man was diagnosed with idiopathic pulmonary fibrosis (IPF), a degenerative disease of the lungs characterised by fibrosis. A 10 mL hUC-MSC intravenous infusion was carried out on the patient with a cell density of 5 × 106 - 1 × 107/mL. The patient was followed for 12 months post-infusion. At the end of the 12-month follow-up, his need for long-term oxygen therapy was reduced substantially, together with improvements in term of quality of life, physical performance and respiratory parameters (lung function, 6 MWD and CT fibrosis score) were all increased from the base line. Throughout the entire study period, no side effects were observed. This study shows the safety and efficacy of transplanting hUC-MSCs to treat IPF and their potential in lung regeneration [35] .

34 patients, aged between 20 and 60 years, with a moderate to severe case of atopic dermatitis (AD) were enrolled in a two-phase clinical study with a follow up of 1 month and 3 months for the first and second phase, respectively [36] .

AD is a genetic, chronic inflammatory disease of the skin that affects between 1% to 3% of adults and 10% to 20% of children [37] . Common symptoms of AD include scratching, pruritus and chronic and/or relapsing eczematous lesions. Social stigma associated with a visible skin disease, the need for frequent visits to a doctor and constant application of messy topical applications further add to the burden of this disease [38] .

Patients in the clinical study were randomly assigned to receive hUC-MSC subcutaneously at either a low dose of 2.5 × 107 cells or a high dose of 5 × 107 cells. An Investigator’s Global Assessment (IGA) score, Eczema Area and Severity Index (EASI) score, Severity Scoring for Atopic Dermatitis (SCORAD) score, serum biomarker levels and adverse effect assessments were all used as end points [36] .

At week 12, a dose-dependent therapeutic effect was observed, with consistent improvements, both from a visual comparison of the symptoms and from the score ranges, as shown below [36] :

・ EASI score range - 0 to 72;

・ IGA score range - 0 to 5;

・ SCORAD score range - 0 to 103.

This study has shown that adults suffering from a moderate to severe AD respond positively to hUCB-MSCs treatment, regardless of the HLA match and with no side effects being experienced.

Gingival recession is the displacement of the gingival margin apically from the cementoenamel junction (CEJ). The resultant root exposure, is not only aesthetically unpleasant, it can also lead to sensitisation and the formation of root caries [39] .

In their clinical study, Zanwar et al. compared the efficacy of human umbilical stem cells seeded on polylactic acid (PLA) and polyglycolic acid (PGA) membranes compared to that of PLA/PGA membranes alone in the treatment of multiple gingival recessions.

14 cases of multiple gingival recession-with a Miller’s Class I or II classification-were randomly selected and divided into the test group (treated with PLA/PGA membrane seeded with human umbilical stem cells) and the control group (treated PLA/PGA membrane alone). Mean gingival recession at the baseline and 6 months post-operation were recorded [40] .

At baseline, the mean gingival recession at 16 and 14 sites in the test and control groups were measured to be at 2.28 mm and 2.14 mm respectively. At 6 months post-surgery, the test group showed a 1.57 mm mean reduction of gingival recession while the control group showed a mean gingival recession of 1.24 mm; with 66% and 57% root coverage, respectively [40] .

This study has therefore shown that, patients treated with PLA/PGA membranes containing the human umbilical stem cells showed a significantly higher mean root coverage compared to patients treated with PLA/PGA membranes alone [40] .

A 26-year-old female patient with primary systemic lupus erythematosus (SLE) and secondary Sjogren’s syndrome (SS) was treated with UC-MSCs, 13 years after diagnosis [41] .

SLE is an inflammatory, autoimmune disorder forming part of the connective tissue disease (CTD) spectrum. The disease has genetic and environmental components which can influence the incidence of the disease. SLE tends to severely limit the patient’s daily activities through pain, fatigue and multiple organ impairment [41] .

SS is another type of CTD, characterised by xerostomia, xerophthalmia and parotomegaly in combination with CTD spectrum pathology [41] .

The UC-MSCs were delivered to the patient intravenously in four injections of 25 million cells each over a span of 3 weeks, together with 0.25 mL GcMAF (Gc protein-derived macrophage activating factor) delivered intramuscularly weekly in combination with vitamin D3 5000 IU/600mg calcium supplementation daily [41] .

Over the year, prior to this treatment, the patient had cycled through a variety of anti-inflammatory drugs and immunosuppressants with limited efficacy [41] .

The treatment was tolerated by the patient with no complications arising. 3 months post-treatment, the patient reported improvements in multi-joint pain and stiffness and began tapering off the medications. 8 months post-treatments, the patient had a complete resolution of all symptoms, showed no complications related to the HU-MSCs treatment and all medications were discontinued [41] .

Further studies need to be carried out to elucidate whether the improvement experienced by this patient was through the combined therapy or due to HU-MSC delivery alone.