Autologous Infusion of Bone Marrow and Mesenchymal Stromal Cells in Patients with Chronic Obstructive Pulmonary Disease: Phase I Randomized Clinical Trial

Figures & data

Figure 1 Schematic representation of sample selection and experimental design.

Figure 2 Cytogenetic analysis of ADSC maintained in culture until the third passage and characterization by immunophenotyping and differentiation of the ADSC and Co-infusion (ADSC and BMMC) groups.

Notes: (A) Expression of surface markers detected using flow cytometry analysis of cultured ADSCs from 10 patients who received ADSCs alone or in co-infusion; (B) Differentiation of ADSCs into adipocytes, chondrocytes and osteocytes from patients of both the ADSC and co-infusion groups. Data from 10 patients who received BMMC infusion (5 patients) or co-infusion (5 patients). (C) Cytogenetic analysis from 10 patients who received ADSCs alone (5 patients) and those who received the co-infusion of BMMCs and ADSCs (5 patients).

Figure 3 Different parameters of pulmonary function by means of spirometry and plethysmography for Control, BMMC, ADSC and Co-infusion (BMMC and ADSC) groups. The data refer to the mean of the 5 patients in each group. (A) FEV₁ (%) post- bronchodilator, (B) FEV/FVC(%), (C) TLC (%), (D) RV(%), (E) DLCO (%), (F) pCO₂.

Abbreviations: FEV₁, forced expiratory volume in first second; FVC, forced vital capacity; forced expiratory FEV₁/FVC ratio; TLC, total lung capacity; VR, residual volume; DLCO, diffusion lung capacity for carbon monoxide; pCO, partial pressure of CO.

Table 1 Different Pulmonary Function Parameters Over 12 Months in Relation to Baseline Data Before Treatment for the Control, BMMC, ADSC and Co-Infusion Groups

Characteristics	Control	BMMC	ADSC	Co-Infusion
Age (years)	59.80 ± 2.86	60.80 ± 5.40	63.20 ± 2.59	65.80 ± 3.60
Sex (Female/Male)	4/1	4/1	4/1	3/2
Body mass index at enrolment	26.05 ± 5.13	24.44 ± 1.73	26.04 ± 2.00	24.68 ± 1.14
Oxygen saturation	94.40 ± 2.41	93.00 ± 2.24	93.20 ± 1.10	93.80 ± 2.59
Pulse rate, per minute	75.20 ± 10.21	94.20 ± 8.14	82.80 ± 4.09	86.80 ± 7.20
sBP, mm Hg	131.60 ± 14.24	134.00 ± 19.49	122.00 ± 23.87	128.00 ± 15.17
dBP, mmHg	77.00 ± 9.75	74.00 ± 21.91	80.00 ± 7.07	78.00 ± 11.40
mMRC	2 (2–2)	2 (1–3)	3 (3–4)	2.5 (1–3)
SGRQ	34 ± 12	28 ± 8	35 ± 15	36 ± 14
6 MWT (m)	388.60 ± 85.52	410.40 ± 39.40	379.00 ± 101.09	406.25±18.01
Plethysmography
FVC (L)	2.21 ± 0.67	1.82 ± 0.74	2.19 ± 0.54	2.54 ± 1.03
FEV1 (L)	1.11 ± 0.35	1.03 ± 0.47	0.90 ± 0.13	1.01 ± 0.16
FEV1 (% predicted)	41.80 ± 7.95	39.60 ± 6.99	38.76 ± 5.74	39.40 ± 6.35
FEV1/FVC (%)	66.20 ± 13.48	64.56 ± 10.83	63.56 ± 15.09	52.00 ± 10.98
TLC	6.18 ± 0.85	5.58 ± 1.59	5.88 ± 1.36	8.36 ± 2.00
TLC (%)	127.60 ± 11.10	121.60 ± 15.16	89.69 ± 51.79	142.50 ± 21.98
RV (%)	215.60 ± 46.63	210.00 ± 26.30	151.11 ± 85.64	233.00 ± 49.30
RV/TLC (%)	195.80 ± 33.80	186.60 ± 23.32	156.83 ± 91.69	183.25 ± 42.85
Raw (%)	164.00 ± 47.81	194.50 ± 80.14	150.18 ± 97.39	151.00 ± 23.45
IC (%)	77±10	77± 16	71±17	80±22
VA (%)	64.1±32.8	67.2±14.2	67.8±12	84±20.6
DLCO (%)	47.60 ± 26.99	35.92 ± 26.92	37.48 ± 36.29	35.60 ± 11.15
DL/VA (%)	58.80 ± 26.38	57.75 ± 33.89	54.11 ± 46.11	40.00 ± 11.07
Blood gas analysis
pO2 (mmHg)	75.26±7.63	68.96±16.89	71.48±3.14	72.3±10
pCO2 (mmHg)	35.86±2.45	36.22±4.1	37±3.45	37.1±3.9
Cardiopulmonary test
VO2peak(L/min)	14±4.6	16.7±7.6	11.1±6.2	13.8±1.8

Abbreviations: sBP, systolic blood pressure; dBP, diastolic blood pressure; mMRC, dyspnea scale; SGRQ, St. George’s Respiratory Questionnaire; 6 MWT (m), 6 Minute Walk Test; FVC, forced vital capacity; FEV₁, forced expiratory volume in one second; TLC, total lung capacity; RV, residual volume; Raw, resistance of the airways; DLCO, diffusion lung capacity for carbon monoxide; AV, alveolar volume; DL/VA specific diffusing capacity; IC, inspiratory capacity; pO₂, oxygen partial pressure; pCO₂, partial pressure of carbon dioxide; VO_2peak, oxygen consumption at peak.

Figure 4  Saint George Hospital Respiratory Disease Questionnaire (SGRQ).

Abbreviations: BMMC, bone marrow mononuclear cells; ADSC, adipose-derived mesenchymal stromal cells.