Parents’ Commitment to Participation in Mesenchymal Stem Cell Donation and Research Demonstrates Extensive Altruism to Other Patients.
Authors: Walraven Anne-Marie , Bernardo Maria-Ester , Brand Anneke , Roelofs Helene , Locatelli Franco , Egeler R. Maarten , Fibbe Willem E. , Ball Lynne M. 
Published: October 2019

Abstract
Mesenchymal stem cells (MSC’s) can be used in the experimental transplant setting for treatment of life threatening GvHD or to improve engraftment. Presently, the European MSC Consortium has three ethically approved multi center clinical protocols in use. MSC’s expanded ex vivo from donor bone marrow are mostly of parental origin. We reviewed donation data from two participating centers, to establish donor commitment, donation and procedural related complications. Parents of children undergoing haploidentical PBSCT or a cord blood transplant were asked to donate 50 cc of bone marrow 4–5 weeks prior to HSCT. Parents of children with non-steroid responsive aGvHD (grade III-IV) were asked at the time of treatment failure. Bone marrow was aspirated either under general or local anesthesia. Haploidentical PBSC donors received in addition 5 days of G-CSF immediately before stem cell harvest. Donors were asked to consider consent for additional MSC’s to be donated for research or use as 3rd party donations for other patients. Donors were cleared for donation by an independent physician. Thirty three donors (14 mothers, 18 fathers, 1 brother) of 34 relatives asked, agreed to donate bone marrow for MSC expansion and all additional uses. One parent whose child died before receiving MSC’s requested they be used for 3rd party donations. Fourty five patients (included 6 adults) were treated with MSC’s (see table 1 for details). Thirty one patients (68%) received MSC’s from a parent, the remaining treatments being 3rd party for acute GvHD. All donors were considered suitable for PBSC or BM donation, although excess weight, mild hypertension and depression were documented in a minority of donors. No adverse events were documented after bone marrow donation, but one parent suffered severe bone pain, requiring opiate analgesia, during G-CSF administration. At 6 weeks follow up no adverse effects were reported. MSC donation either alone or in combination with stem cell mobilization can be achieved without major problems. Parental donor commitment is definitely related to the needs of the child. However, donor altruism to include other unknown patients including adult recipients was uniformly evident in our studies. Donation of stem cells for parents is a stressful situation and requests for multiple donations of various types of cell products can raise questions about medical and ethical considerations. Our protocols show that well informed parents have a propensity to commit to others needs as well as their offspring’s. It is therefore essential when introducing experimental treatments to establish a balance between donors commitment and patient needs.
Table 1. Patient and donor characteristics PATIENTS n=45 OUTCOME DONORS n=33 Male 29 21 alive 19 Female 16 12 alive 14 Age (range years) 7.0 (0.6–16.4) 38 (26–53.3) Hematological malignancy 35 Immune deficiency 3 Others 7 Haplo+ MSC 21 15 alive Own child donations Cord + MSC 9 1 rejection 1 death Own child donation aGvHD 15 CR in 11 patients 14/15 3rd party donations Complications 2 a GvHD (grade I) Severe pain 1 donor Infections 14 patients Platelet tx in 4 haplo-donors